PubMed is a service of the U.S. National Library of Medicine that includes over 18 million citations from MEDLINE and other life science journals for biomedical articles back to 1948. PubMed includes links to full text articles and other related resources. This is a valuable resource that we can use to obtain information on peripheral neuropathy (PN). There are over 100 medical articles per month written on PN.

CUMULATIVE ANNOTATED BIBLIOGRAPHY

Of SELECTED ARTICLES from the NEUROPATHY LITERATURE 2009- 11/2014

 PERIPHERAL NEUROPATHY LITERATURE REVIEW ARCHIVE

 William B. Donovan MD writes the Peripheral Neuropathy Literature Review for Neuropathy Hope, the monthly newsletter of the Pacific Chapter of the Neuropathy Association (PCNA). He reviews approximately a hundred medical articles on peripheral neuropathy (PN) indexed by the National Library of Medicine (NLM) a month. Those articles that would appear to be most interesting to neuropathy patients are selected and summarized. They emphasize prevention, evidence-based treatment, alternative treatment and cutting edge research. The above summaries appearing over the past several years are included in this archive.

 

Each summarized article is preceded by a “PMID”, a unique PubMed Identification Number. In order to obtain more information on any particular summarized article, its PMID may be entered into the “for” search bar of PubMed—and then click “GO”. The PubMed website is available at:

www.ncbi.nlm.nih.gov/sites/entrez

 

Dr. Donovan has encouraged readers to familiarize themselves with this website—either on their own computer, or one belonging to a friend, or the public library. In this way they will be able to expand on the leads given in his column.

 

As an example, some of the PMIDs that can be entered include the following:

  • 18021866 (prevention of PN due to shingles);
  • 15616239 (promotion of nerve regeneration);
  • 17696592 (prevention of chemotherapy induced PN).

 

Note: Dr. Donovan is a physician retired from the practice of chronic pain management. He is a PN patient and a member of the Monterey CA support groups.

 

 

  • 8469412 This study demonstrates that DMSO (dimethylsulfoxide) in a concentration of 5-7% completely blocks the C pain fibers in cat sural nerve, explaining the analgesic effect on deeper structures from the topical application of 75% DMSO solution to the skin.

 

  • 8721469 A Dutch randomized controlled trial reporting significant (p<0.01) reduction of VAS pain scores in 32 patients with reflex sympathetic dystrophy, an extremely painful neuropathic pain condition thought to be related to peripheral neuropathy. The treatment group received DMSO 50% in a greasy cream topically 5 times a day for 2 months.

 

  • 9671841 An early case report of peripheral neuropathy characterized by burning sensation in both feet, decreased light touch, loss of position sense and diminished ankle reflexes after two years of statin therapy. The symptoms improved on withdrawal of the statin, but recurred on rechallenge with the original and two other statins as well as niacin.

 

  • 10850865 A Mayo Clinic study of non-diabetic lumbosacral radiculoplexus neuropathy, found to be similar to the diabetic form with nerve degeneration due to microvasculitis. This under-recognized multifocal disorder is characterized by weight loss and asymmetrical lower extremity findings: pain, allodynia weakness, atrophy, and autonomic features. It is responsive to intravenous corticosteroids.

 

  • 12373705 This study of ketamine (0.25-1.5%) ointment reports local anesthetic effect in the early dystrophic stage of complex regional pain syndrome. Effect is attributed to the drug’s blockade of the NMDA receptor.

 

  • 12455197 This randomized double-blind placebo controlled parallel group multicenter study of 333 diabetic neuropathy patients with baseline impaired electrophysiology, were administered acetyl-L carnitine, 1000mg intravenously for 10 days, and 2000mg orally for 355 days. There were large significant improvements of the sural, peroneal and ulnar nerves in both velocity and amplitude. VAS pain scores were reduced 39% compared to 8% in the placebo group.

 

  • 12707455 This study reports on the non-randomized, uncontrolled treatment of 16 post-herpetic neuralgia patients with the addition of 5mg/ml ketamine gel, with reduction in pain levels from severe to either moderate or mild.

 

  • 12722128 A detailed discussion from King Saud University of the medical literature and beneficial effects of the Indian herb Nigella Sativa (kalonji), including analgesia.

 

  • 12809967 Doctor E.L. Tobinick reports two cases of chronic, severe, cervical, discogenic pain whose necks he injected subcutaneously with etanercept (Enbrel®) that were pain-free at one year.

 

  • 14305159 This paper from the University of Oregon Medical school reports on the relief of chronic intractable pain with the daily topical application of 90% DMSO in 9 0f 11 patients suffering from tic doloreaux.

 

  • 14321156 This 1965 article from the Department of Surgery, University of Oregon Medical School, reports on an unrandomized open trial of DMSO 90% with eight amputees suffering with phantom limb pain, six of whom experienced relief of pain initially for four hours, increasing in duration over the 3-6 months of the study.

 

  • 15101968 This article from Hahnemann School of Medicine reports 5 cases of neuropathic pain responding within 5 minutes following the topical application of 10% ketamine gel, with a 53-100% reduction in NAS pain scores, without significant side effects.

 

  • 15115710 A Swiss study of acute, severe sciatica pain, comparing subcutaneous etanercept (Enbrel®) in the treatment group with intravenous methylprednisolone (Medrol®) in the control group, found a statistically significant improvement in the treatment group.

 

  • 15265252 This retrospective uncontrolled study by Tobinick of 143 patients with chronic treatment-refractory disc-related pain, treated with etanercept (Enbrel®) 25mg.injected subcutaneously directly over the affected spine, revealed significant (p<0.0001) reduction in pain, although half the group were non-responders.

 

  • 15616239 A randomized placebo controlled study of 1257 patients with diabetic neuropathy who were administered 1000mg acetyl-L carnitine daily over 52 weeks. Significant improvement was seen in pain, increased number of sural nerve fibers and nerve clusters in addition to improved vibratory perception, related to proprioception and balance

 

  • 15726875 A randomized placebo controlled double blind study of diabetics (Types I and II) with neuropathy. The treatment group was given the lipid-soluble prodrug of thiamine (B-1), benfotiamine100mg four times a day orally over a three-week period. There was a statistically significant decrease in neuropathy score, especially pain.

 

  • 15793206 This is a comprehensive outline by the American Diabetes Association of the various forms that diabetic neuropathy can take: sensory, sensorimotor, focal, multifocal and autonomic, including multiple gastrointestinal, genitourinary, and circulatory symptoms. Suggestions for evaluation and management are given.

 

  • 16581329 A systematic review of 16 case reports of symptoms of peripheral neuropathy developing within 1-2 months of initiating statin therapy and resolving after discontinuing the drug. The incidence of neuropathy attributable to statin use, however, is estimated at only 12 per 100,000 person years of treatment.

 

  • 17065669 The SYDNEY 2 trial with distal symmetric neuropathy in diabetics found that alpha lipoic acid 600mg daily for 5 weeks decreased Total Symptom Score by over 50%.

 

  •  17696592 An Italian article reviewing experimental evidence of acetyl-L-Carnitine counteracting the neurotoxicity of cancer chemotherapy agents and promoting recovery of nerve conduction and elevation of pain threshold.

 

  • 17713854 An animal study from Trakya University showing decreased myelin sheath breakdown in diabetic sciatic nerves following treatment with Nigella Sativa.

 

  • 17875242 A study from Spain found that, compared to gabapentin (Neurontin®), pregabalin (Lyrica) was more cost-effective with greater and faster pain reduction.

 

  • 17883740 A Johns Hopkins study of neuropathic pain found over a third reduction in pain and increase in daytime activity with the use of transdermal fentanyl (Duragesic®).

 

  • 17885349 A Stanford study demonstrating decreased neuropathic pain in older more severe cases following intravenous lidocaine (Xylocaine®).

 

  • 17909094 Genetic research with nerve growth factor.

 

  • 17914029   A study by CDC of adult diabetics showing PN to be associated with low levels of polyunsaturated fatty acid in the diet.

 

  • 17920770 Treatment of neuropathic pain with gabapentin (Neurontin®), pregabalin (Lyrica®), tricyclic antidepressants, dual uptake inhibitors, and lidocaine (Xylocaine®) patch.

 

  • 17943857 In a Cochrane Database study of 61 trials of antidepressants for neuropathic pain, it was concluded that venlafaxine (Effexor®) and tricyclic antidepressants are effective.

 

  • 17977931 Although we all know of PN cases who have claimed benefit from Anodyne® monochromatic infrared photo energy treatment, This TAMU double-blind, randomized, sham-controlled clinical trial failed to show significant benefit for sensory neuropathy.

 

  • 18021866 Prevention of shingles neuropathy.

 

  • 18050220 A review of tumor necrosis factor-alpha blocking agents in the treatment of nerve root pain associated with disc herniation, concluding that sciatica is caused by a combination of mechanical and chemical stimulation of the nerve root.

 

  • 18085141 A study from Sichuan demonstrating more post-herpetic pain alleviation from ear point taping and pressing combined with acupoint injection than Western medication.

 

  • 18178525 The ICE Study,”…the largest reported trial of any CIDP (chronic inflammatory demylinating polyradiculoneuropathy) treatment, shows the short-term and long-term efficacy and safety of IGIV-C (intravenous immune globulin) and supports use of IGIV-C as a therapy for CIDP.”

 

  • 18262450 a double-blind placebo-controlled study at King’s College Hospital found that controlled-release oxycodone (Oxycontin®) added to gabapentin (Neurontin®) reduces diabetic neuropathic pain by a third, and improves sleep quality.

 

  • 18403272 A UC Davis double blind, placebo- controlled crossover study of neuropathic pain demonstrated analgesic response to smoking 3.5% as well as 7% cannabis (marijuana).

 

  • 18413214 Venlafaxine (Effexor®) is a combination norepinephrine-serotonin uptake inhibitor like duloxetine (Cymbalta®), the latter approved for use with peripheral neuropathy by the FDA. This study found venlafaxine to be safe, effective and well tolerated as a treatment for the pain of distal symmetrical sensorimotor polyneuropathy.

 

  • 18474189 A review of mirror visual feed back (tricking oneself into seeing the unaffected body part on the affected side of the body) as a way of decreasing neuropathic pain and normalizing movement.

 

  • 18541884 A study at Mt. Sinai Medical Center found that the application of a high concentration capsaicin dermal patch desensitized cutaneous pain receptors in HIV-associated distal sensory neuropathy.

 

  • 18600579 A discussion from the University of Toronto of fish consumption, omega-3 polyunsaturated fatty acids and docosahexaenoic acid (DHA) in the prevention and treatment of neurological disorders.

 

  • 18636234   A meta-analysis by Wake Forest University demonstrated increased functionality and chronic neuropathic pain relief from the H-Wave device manufactured by Electronic Waveform Lab.

 

  • 18646102 A review of the treatment of meralgia paresthetica (pain in the lateral thigh) from Charring Cross Hospital revealed over 80% response to either injection with local anesthetic/corticosteroid, or surgery; however, another study reported a 69% spontaneous recovery, without treatment.

 

  • 18646138 This Johns Hopkins review of the Cochrane Data Base of 142 studies in respect to symmetrical diabetic peripheral neuropathy “…. failed to identify a single randomized controlled trial or any well designed prospective study controlling for the non-operated limb that showed improvements in predefined points after decompressive surgery.

 

  • 18660651 A review of recent studies indicating the role of tumor necrosis factor-alpha from the injured intervertebral disc as the cause of inflammation and decreased nerve conduction velocity in sciatica, and the possibility of the tnf-alpha blocker, etanercept (Enbrel®), reversing the progression of this process.

 

  • 18673529 An Oxford study of fibromyalgia and diabetic neuropathy showed at least 50% pain reduction over 12 weeks for duloxetine (Cymbalta®) compared to placebo.

 

  • 1868812 UC Santa Barbara study of Cannabis (marijuana) for neuropathic pain.

 

  • 18774507 This Johns Hopkins review of three randomized controlled studies of 776 pregabalin (Lyrica®) and 258 controls of painful diabetic peripheral neuropathy found over four times the likelihood of at least 50% improvement with the active drug.

 

  • 18796160   An Albert Einstein College of Medicine study of painful diabetic neuropathy showing over twice the response rate for pregabalin (Lyrica®) at 49%, compared with placebo.

 

  • 18940920   A summary of studies done showing decreased pain and increased nerve regeneration in diabetic PN with acetyl-L-carnitine.

 

  • 19004197   A Guangzhou University study comparing the effectiveness of acupuncture plus acupoint-injection vs. oral carbamazepine (Tegretol®), for occipital neuralgia, with the former being more effective.

 

  • 19027875 A descriptive article written by E.L. Tobinick, the physician who patented a technique involving the injection of etanercept (Enbrel®) subcutaneously over the spine, thence absorbed into the cerebrospinal venous plexus, resulting in the inhibition of tumor necrosis factor, which is hypothesized to cause intervertebral disc-related pain.

 

  • 19141719 A randomized study of diabetic neuropathy patients, 89 treatment cases and 78 controls, demonstrated that silicon orthotics protected the feet from the development of painful hyperkeratotic lesions.

 

  • 19160200 Cochrane Database study of effectiveness of IVIg for CIDP

 

  • 19208243 Meta-analysis of duloxetine (Cymbalta®) vs. pregabalin (Lyrica®) for peripheral neuropathy.

 

  • 19224814 An evaluation of lidocaine (Xylocaine®) 8% spray for post-traumatic peripheral neuropathy found significant pain relief.

 

  • 19242524 Recent research has been exploring the possibility of transporting analgesic chemicals to the dorsal horn of the spinal cord, where the peripheral pain nerves enter the central nervous system. In order to transport these chemicals—enkephalin, endorphin, glutamic acid decarboxylase—rats have been infected with genetically engineered, non-replicating herpes simplex virus, which typically resides in the nerves of the dorsal horn. This complex, novel approach was reported to be safe in human trials at the 2011 meeting of the American Academy of Neurology.

 

  • 19246421 In a double blind crossover study in Taipei of botulinum toxin type A for diabetic neuropathy, there was significant improvement at 3 months post-injection.

 

  • 19252116 Mayo study of shingles prevention with anti herpes zoster vaccine

 

  • 19277838 An Italian study of CT-guided pudendal nerve block for pudendal neuralgia achieved relief of anoperineal pain, 92% at 12 months.

 

  • 19243312   A University of Leicester review of studies demonstrating prevention and amelioration of diabetic neuropathy with proinsulin C-peptide.

 

  • 19301378 An extensive Columbia University review of chronic demylinating polyradiculoneuropathy (CIDP), emphasized well-documented response to IVIg, plasmapheresis and corticosteroids—as well as lesser evidence supporting other agents: cyclophosphamide, rituximab, azothioprine, cyclosporine, interferon, fludarabine, mycophenolate, mofatil, and etanercept.

 

  • 19301937   A study from the University of Schleswig- Holstein comparing oral pregabalin (Lyrica®) with lidocaine (Xylocaine®) 5% medicated plaster found that the efficacy was comparable, but there were 90% fewer adverse events with the local treatment.

 

  • 19317819 A Japanese study of diabetic patients found that those with neuropathy had increased levels of vascular endothelial growth factor (VEGF), the same agent that is involved in diabetic retinopathy and wet age-related macular degeneration.

 

  • 19387178   A Johns Hopkins study of sciatica showing at least a 50% reduction in pain for the majority of patients at six months following nerve root injection with etanercept (Enbrel®).

 

  • 19406920 A study of over 5000 participants from community surveys in Singapore demonstrated that peripheral neuropathy incidence increased gradually with the level of fasting blood sugar, even at levels below the threshold for diabetes mellitus diagnosis.

 

  • 19432499 In a double-blind placebo-controlled multinational trial with post-herpetic neuralgia, improvement of pain, allodynia, quality of life and sleep was achieved with 5% lidocaine (Xylocaine®) plaster applied up to 12 hours daily.

 

  • 19499849 A Neapolitan study of 112 with carpal tunnel syndrome revealed significant improvement in symptoms and function when multivitamin controls were compared with a combination of alpha-lipoic acid 600mg. plus gamma-linolenic acid 360mg. daily.

 

  • 19555786 Chronic abdominal wall pain due to peripheral nerve impingement, often mistaken for intra-abdominal pathology, can be diagnosed by local anesthetic block of trigger points, and relieved by surgically releasing the nerve that is trapped by the muscle sheath.

 

  • 19557864 It is hypothesized that reflex sympathetic dystrophy, now known as complex regional pain syndrome (pain, hypersensitivity, sweat, edema, discoloration), may be a posttraumatic small fiber peripheral neuropathy.

 

  • 19588419 A review of the University of Oxford of 19 randomized control trials of pregabalin (Lyrica®) 600mg daily showed a minimum number of patients needed to treat (NNT), to achieve at least 50% pain relief was 5.6 for diabetic neuropathy and 5.0 for post-herpetic neuralgia.

 

  • 19590482 A study from Taiwan of carpal tunnel syndrome (wrist pain) showed no difference between those treated with corticosteroid and those receiving acupuncture.

 

  • 19655114 An extremely detailed monograph outlining possible mechanisms whereby nerve injury results in chronic pain—mediated by neuroinflammation, release of inflammatory cytokines, followed by hypersensitivity of the dorsal root ganglia, peripherally and later centrally in the dorsal horn of the spinal cord. Possible intervention using cytokine antibodies, e.g., anti- tumor necrosis factor alpha, is suggested.

 

  • 19664690 This is an excellent but very detailed and technical review by the Linus Pauling Institute of alpha lipoic acid, including studies using it as a treatment of peripheral neuropathy.

 

  • 19703730 An Australian study of the local application of 10% Ketamine cream (NMDA antagonist) in patients with complex regional pain syndrome, inhibited allodynia (painful response to non-pain stimuli).

 

  • 19703730 This is a study of 20 patients with posttraumatic complex regional pain syndrome, thought to be a form of peripheral neuropathy. The application of 10% racemic ketamine in pluronic lecithin organogel inhibited allodynia (light brushing producing intense pain) in these exquisitely sensitive patients.

 

  • 19789071 Use of sodium channel blockade to treat peripheral neuropathy dates to Freud’s use of cocaine for trigeminal neuralgia, and has been expanded to include lidocaine (Xylocaine®), phenytoin (Dilantin®), lacosamide (Vimpat®), carbamazepine (Tegretol®), lamotrigine (Lamictal®), mexiletine (Mexitil®), amitriptyline (Elavil®), and duloxetine (Cymbalta®).

 

  • 19796802 This study at Queen’s University, Ontario, found that the antidepressant nortriptyline (Pamelor®) in combination with the anticonvulsant gabapentin (Neurontin®) controlled neuropathic pain more effectively than either medication alone.

 

  • 19801049 Under the auspices of the International Association for the Study of Pain, a consensus process developed evidence-based guidelines for the management of neuropathic pain, recommending tricyclic and dual uptake inhibitors of serotonin and norepinephrine, e.g., duloxetine (Cymbalta®), gabapentin (Neurontin®) and pregabalin (Lyrica®), and topical lidocaine (Xylocaine®) as first line treatments for neuropathic pain.

 

  • 19821395 A Cochrane database review of controlled trials of 2,220 patients prescribed duloxetine (Cymbalta®) for neuropathic pain (both neuropathy and fibromyalgia) found “moderately strong” evidence of effectiveness for doses between 60 mg. and 120 mg. daily.

 

  • 19846797 This prospective case-control study comparing Type 2 diabetics experiencing peripheral neuropathy who received metformin (Glucophage®) with those who did not, found strong correlation between cumulative metformin dose and both electrophysiological parameters and Neuropathy Impairment Score. Malabsorption of vitamin B12 due to metformin was suggested as the cause.

 

  • 19921145 A randomized, controlled study of diabetics with varying degrees of peripheral neuropathy were given twice weekly physiotherapeutic group training in gait and balance exercises as well as function-oriented strengthening over twelve weeks. At six months there was significant improvement in balance, gait, mobility and strength

 

  • 20113411 A randomized double-blind, controlled study of post-herpetic neuralgia (shingles) comparing an 8% capsaicin dermal patch with a 0.04% control, found change in pain score of –33.8% compared to +4.9% at the end of twelve weeks.

 

  • 202236172 A double blind randomized controlled study of pregabalin (Lyrica®) 150-600 mg. daily found significant improvement in pain-related sleep interference (p < 0.001) with relief of post-traumatic peripheral neuropathic pain.

 

  • 20447305 A randomized, double blind, placebo-controlled trial of agmatine sulfate (decarboxylated amino acid arginine) 2.670 gm. daily for 14 days in cases of painful lumbar disc-associated radiculopathy, demonstrated significant improvement in pain and quality of life.

 

  • 20458651 A review of 23 studies of 5% lidocaine (Xylocaine®) medicated plaster to manage painful diabetic peripheral neuropathy, found fewer adverse events, but comparable effectiveness compared with amitriptyline (Elavil®), capsaicin, gabapentin (Neurontin®), and pregabalin (Lyrica®). 

 

  • 20460982 This article from Cook County Hospital describes paraneoplastic neurological syndrome, including peripheral neuropathy, which can occur as a result of occult cancer.

 

  • 20487567 This is a double blind randomized placebo controlled study from Louisiana State University assessing the topical oil, Neuragen PN®, in the treatment of neuropathic pain. Neuragen PN® resulted in significantly greater pain reduction (p < 0.05). 93.3% of treated patients compared to controls experienced pain relief within 30 minutes.

 

  • 20503464 An LSU study of 25 peripheral neurology patients over a 24 week course of tai chi instruction, found large improvement in plantar sensation, 6 minute walk, timed up and go, and leg strength.

 

  • 20594588 The 77 site ACCORD controlled study of Type2 diabetes found that tighter control of blood sugar (HbA1c target <6%) found improvement in light touch and ankle jerk in those with peripheral neuropathy.

 

  • 20599049 A randomized double blind, sham-controlled study of magnetic disks applied for six weeks to the wrists of carpal tunnel syndrome patients, showed no statistically significant benefit in terms of nerve conduction or pain.

 

  • 20805210 A study from McGill University of posttraumatic or post-surgical patients with chronic neuropathic pain. A 25 mg dose of 9.4% smoked THC (marijuana) resulted in improved quality of sleep and decreased time to get to sleep. Adverse effects included cough, dry eyes, burning sensations, numbness and dizziness.

 

  • 20921842 This article discusses duloxetine (Cymbalta®) an antidepressant that blocks the reuptake of both norepinephrine and serotonin, and is approved by the FDA for treatment of peripheral neuropathy. Probable mechanism of action is the facilitation of descending pain inhibition pathways. Relief of other painful conditions, including fibromyalgia, has also been achieved.

 

  • 21127770 This article reminds us that Lyme disease, following a tick bite, and typically presenting with an expanding rash and arthritis, is a multisystem infection often causing painful neuropathies of both the cranial and peripheral nerves.

 

  • 21134121 According to a randomized controlled study of botulinum toxin (Botox®) injection for post-herpetic neuralgia (shingles), both pain and insomnia improved significantly. Opiate usage dropped 21% in the treatment group compared to the placebo group, which remained between 53-67%.

 

  • 21206429 Following twice-daily administration of a combination of methylfolate 3mg, methylcobalamine 2mg, and pyridoxyl 5’-phosphate 35mg to 20 Type II diabetics with peripheral neuropathy, 1 point tactile and 2-point tactile (discrimination) examination showed improvement in cutaneous sensation in the feet.

 

  • 21210541 In a study of 596 patients with Type 2 diabetes, the investigators found that those with two or more complications, especially neuropathy or nephropathy, were at over twice the risk for clinical depression.

 

  • 21321947 Although previously thought to be due to thiamine deficiency, alcohol neuropathy is not reversible by vitamin B1, and, therefore, should be considered a toxic neuropathy.

 

  • 21336050 A Mayo Clinic study of transcranial magnetic stimulation of skull over the right dorsolateral prefrontal cortex of 9 subjects with refractory neuropathic pain, found that over a third had at least 50% reduction in pain. rTMS is being used more commonly for clinical depression. These patients had an average pain rating of 7.3, but no significant depression.

 

  • 21372279 A review of nine reports, 69 patients, receiving local anesthetic and corticosteroid nerve blocks for neuralgia, with 30 achieving complete pain relief, and 10 over 50% relief.

 

  • 21412914 This Cochrane Data Base review of 14 studies with 2831 patients evaluated gabapentin (Neurontin®) treatment of chronic neuropathic pain. Compared to placebo (17%), “substantial benefit” was achieved with 31%. Withdrawal from the study due to adverse event occurred in 12%.

 

  • 21425512 A paper from the Anaesthesia Department, Princess Margaret Hospital, Hong Kong describing meralgia parestheticum, lateral femoral cutaneous nerve entrapment neuropathy of the anterolateral thigh. Blockade with local anesthetic and steroid is both diagnostic and therapeutic.

 

  • 21561371 An article from Seoul describing a controlled, twice weekly, 8- week balance training program for older adults with diabetic neuropathy. Statistically significant improvement compared to controls was found in the following: dynamic balance, functional reach, timed up and go, trunk repositioning, and 10-m walking time.

 

  • 21719618 This study compared duloxetine (Cymbalta®) with pregabalin (Lyrica®) in the treatment of peripheral neuropathy pain in diabetics unresponsive to gabapentin (Neurontin®). Duloxetine was not statistically more effective than pregabalin. Side effects with duloxetine included insomnia, sweating, and appetite loss; pregabalin side effect was peripheral edema.

 

  • 21763099 This is a randomized, controlled study comparing guideline-based drug management of neuropathic pain with Scrambler (electrocutaneous nerve stimulation device) therapy in ten daily sessions. At one month the Scrambler group improved on the Visual Analog Scale with a score of 91% compared to 28% in the drug group.

 

  • 21767768 An MGH paper, Neuropathic Itch, describes dysfunction of the itch-sensing neurons caused by shingles, small fiber polyneuropathy, and radiculopathy. Although this condition is refractory to steroids, antihistamine and analgesics, application of local anesthetics has been helpful.

 

  • 21769070 The more bioavailable forms of the B vitamins L-methylfolate (folic acid), methylcobalamine (B-12) and pyridoxyl5”-phosphate (B-6) have been demonstrated singly to reverse the effects of neuropathy. This study administered all three of the provitamins orally twice a day to eleven Type II diabetics with peripheral neuropathy for six months. Calf punch biopsy showed an increase of epidermal nerve fiber density in 73% and both reduced frequency of paresthesias and /or dysesthesias.

 

  • 21775755 This is the four- year, multicenter, randomized, controlled, NATHAN I study of alpha lipoic acid in chronic, mild to moderate, diabetic, distal, symmetric, sensorimotor polyneuropathy. NATHAN I demonstrated clinically meaningful decrease in the progression of neuropathic symptoms.

 

  • 21807565 A French study demonstrating that rTMS (repetitive transcranial magnetic stimulation) significantly reduces neuropathic pain in 79% of peripheral neuropathy patients.

 

  • 21814197 A Mayo Clinic article reviewing therapy of chemotherapy-induced peripheral neuropathy (CIPN). The strongest evidence for prevention supports the use of intravenous calcium, magnesium and glutathione. The most effective agents for treatment appear to be serotonin/norepinephrine reuptake inhibitors.

 

  • 21998121 This is a randomized, controlled study of patients with acute sciatica. In the group treated with two subcutaneous injections of adalimubab (a tumor necrosis factor, alpha), 28% required surgery within three years, whereas 56% of the control group required surgery.

 

  • 22050401 This Kuwaiti study found that those Type 2 diabetics with peripheral neuropathy had significantly lower vitamin D levels than those without. Further study assessing vitamin D as a preventive is suggested.

 

  • 22028723 This is a case report involving the progressive addition of topical amitriptyline 5% cream, 10% ketamine cream, and DMSO 50% three times a day with reduction of pain from 26/45 to 6/25 on the McGill Pain Questionnaire.

 

  • 22082324 This article from the School of Pharmacy Practice, University of Puerto Rico, discusses what dietary supplements can be used to correct the metabolic defects that can contribute to the progression of diabetic peripheral neuropathy. Increased polyol pathway, nitric oxide deficit, increased homocysteine levels are listed as the underlying causes. Suggestions for remediation include alpha-lipoic acid, acetyl-L-carnitine, L-methyl folate, benfotiamine and pyridoxyl-6-phosphate.

 

  • 22133325 This review article presents evidence from a number of studies revealing significantly increased relief of neuropathic pain from a pairing of either gabapentin (Neurontin®) or pregabalin (Lyrica®), and an opioid, cox inhibitor, or antidepressant—greater than could be achieved with any of these agents singly.

 

  • 22028723 This is a case report involving the progressive addition of topical amitriptyline 5% cream, 10% ketamine cream, and DMSO 50% three times a day with reduction of pain from 26/45 to 6/25 on the McGill Pain Questionnaire.

 

  • 22146780 A Hamburg Medical Centre study of chemotherapy-induced peripheral neuropathy showed improvement of nerve conduction velocity in 5 out of 6 patients treated with acupuncture for 10 weeks. Although not randomized, only one patient in the control group improved.

 

  • 22307048 A review of itches that are neuropathic and not dermatologic in origin, resulting from lesions in the brain, spinal cord, and peripheral nerves. Itching due to small fiber neuropathy may respond to topical or systemically administered mexiletine (Mixitil®), local anesthetics, topical tacrolimus (Prograf®), or gabapentin (Neurontin®).

 

  • 22313580 Neuropathic pain due to peripheral nerve injury as measured by pain rating scales at three months post block, responds much better to the combination of the corticosteroid depo-methylprednisolone (Depo-Medrol®) and lidocaine (Xylocaine®) than lidocaine alone.

 

  • 22442436 A multicenter, randomized, controlled study of chronic inflammatory demyelinating polyradiculopathy (CIDP) comparing bimonthly pulses of dexamethasone (Decadron®) with eight months of daily prednisolone (Medrol®), achieving cure or long-term (4.5 year) remission in approximately a quarter of the cases.

 

  • 22480279 Of those neuropathy patients refractory to gabapentin (Neurontin®) therapy, 42.5% experienced over 50% pain reduction after switching to pregabalin (Lyrica®).

 

  • 22500483 This is an optimistic Mayo review of the use of Ketamine, an NMDA antagonist originally used as an anesthetic, that is now used as an analgesic for the management of refractory neuropathic pain, available in oral, intravenous, subcutaneous, and topical forms.

 

  • 22502623 This study of chronic herpes zoster (shingles) pain found that alternative/Chinese medicine (acupuncture, 1% procaine injections, cupping, bleeding and herbs) reduced pain on a 10-point scale at 3 weeks from 7.5 to 2.3 in the treatment group compared to 7.8 to 7.2 in the controls.

 

  • 22518362 This McGill study of neuropathic pain found that the tendency to catastrophize (exaggerate the negative outlook toward one’s illness) predicted poorer response to treatment, in this case, topical analgesia.

 

  • 22538308 A Columbia University study found over a 38% prevalence of peripheral neuropathy both in patients with celiac disease and inflammatory bowel disease, compared to 20.5% prevalence in the population (staff and visitor controls).

 

  • 22606679 Canadian Pain Society guidelines, with reservations, support the following evidence-based interventional treatments for neuropathic pain: spinal cord stimulation, intravenous infusions, epidural injections and nerve blocks. The article reviews over forty studies in this literature.

 

  • 22683276 A randomized controlled study of topical 0.1% clonidine (Catapress®) gel with painful diabetic neuropathy, found significant reduction in the level of foot pain among those patients who were pain-sensitive to capsaicin.

 

  • 22696371 Diabetic neuropathy affects 10% of diabetics at diagnosis, and 40-50% after 10 years. A Cochrane database review of 17 studies showed that enhanced control of blood sugar resulted in reduced nerve conduction and vibration threshold abnormalities in Type I diabetes mellitus.

 

  • 22701355 This paper discusses the experimental use of transplanted bone marrow derived cells as a source of cultured Schwann Cells that can be used with conduits to induce nerve grafts to repair injured peripheral nerves.
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Each summarized article is preceded by a “PMID”, a unique PubMed Identification Number. In order to obtain more information on any particular summarized article, its PMID may be entered into the “for” search bar of PubMed—and then click “GO”. The PubMed website is available at:

www.ncbi.nlm.nih.gov/sites/entrez

 

Dr. Donovan has encouraged readers to familiarize themselves with this website—either on their own computer, or one belonging to a friend, or the public library. In this way they will be able to expand on the leads given in his column.

As an example, some of the PMIDs that can be entered include the following:

  • 18021866 (prevention of PN due to shingles);
  • 15616239 (promotion of nerve regeneration);
  • 17696592 (prevention of chemotherapy induced PN).

 Note: Dr. Donovan is a physician retired from the practice of chronic pain management. He is a PN patient and a member of the Monterey CA support groups.

  • 10850865 A Mayo Clinic study of non-diabetic lumbosacral radiculoplexus neuropathy, found to be similar to the diabetic form with nerve degeneration due to microvasculitis. This under-recognized multifocal disorder is characterized by weight loss and asymmetrical lower extremity findings: pain, allodynia weakness, atrophy, and autonomic features. It is responsive to intravenous corticosteroids.

 

  • 12722128 A detailed discussion from King Saud University of the medical literature and beneficial effects of the Indian herb Nigella Sativa (kalonji), including analgesia.

 

  • 12809967 Doctor E.L. Tobinick reports two cases of chronic, severe, cervical, discogenic pain whose necks he injected subcutaneously with etanercept (Enbrel®) that were pain-free at one year.

 

  • 15115710 A Swiss study of acute, severe sciatica pain, comparing subcutaneous etanercept (Enbrel®) in the treatment group with intravenous methylprednisolone (Medrol®) in the control group, found a statistically significant improvement in the treatment group.

 

  • 15265252 This retrospective uncontrolled study by Tobinick of 143 patients with chronic treatment-refractory disc-related pain, treated with etanercept (Enbrel®) 25mg.injected subcutaneously directly over the affected spine, revealed significant (p

 

  • 15616239 A study of acetyl-L-carnitine (ALC) 1000mg three times daily for 52 weeks with peripheral neuropathy patients found improvement in pain, vibratory sense and nerve regeneration.

 

  • 17065669 The SYDNEY 2 trial with distal symmetric neuropathy in diabetics found that alpha lipoic acid 600mg daily for 5 weeks decreased Total Symptom Score by over 50%.

 

  •  17696592 An Italian article reviewing experimental evidence of acetyl-L-Carnitine counteracting the neurotoxicity of cancer chemotherapy agents and promoting recovery of nerve conduction and elevation of pain threshold.

 

 

  • 17713854 An animal study from Trakya University showing decreased myelin sheath breakdown in diabetic sciatic nerves following treatment with Nigella Sativa.

 

  • 17875242 A study from Spain found that, compared to gabapentin (Neurontin®), pregabalin (Lyrica) was more cost-effective with greater and faster pain reduction.

 

  • 17883740 A Johns Hopkins study of neuropathic pain found over a third reduction in pain and increase in daytime activity with the use of transdermal fentanyl (Duragesic®).

 

  • 17885349 A Stanford study demonstrating decreased neuropathic pain in older more severe cases following intravenous lidocaine (Xylocaine®).

 

  • 17909094 Genetic research with nerve growth factor.
  • 17696592 An Italian article reviewing experimental evidence of acetyl-L-Carnitine counteracting the neurotoxicity of cancer chemotherapy agents and promoting recovery of nerve conduction and elevation of pain threshold.

 

  • 17914029   A study by CDC of adult diabetics showing PN to be associated with low levels of polyunsaturated fatty acid in the diet.

 

  • 17920770 Treatment of neuropathic pain with gabapentin (Neurontin®), pregabalin (Lyrica®), tricyclic antidepressants, dual uptake inhibitors, and lidocaine (Xylocaine®) patch.

 

  • 17943857 In a Cochrane Database study of 61 trials of antidepressants for neuropathic pain, it was concluded that venlafaxine (Effexor®) and tricyclic antidepressants are effective.

 

  • 17977931 Although we all know of PN cases who have claimed benefit from Anodyne® monochromatic infrared photo energy treatment, This TAMU double-blind, randomized, sham-controlled clinical trial failed to show significant benefit for sensory neuropathy.

 

  • 18021866 Prevention of shingles neuropathy.

 

  • 18050220 A review of tumor necrosis factor-alpha blocking agents in the treatment of nerve root pain associated with disc herniation, concluding that sciatica is caused by a combination of mechanical and chemical stimulation of the nerve root.

 

  • 18085141 A study from Sichuan demonstrating more post-herpetic pain alleviation from ear point taping and pressing combined with acupoint injection than Western medication.

 

  • 18178525 The ICE Study,”…the largest reported trial of any CIDP (chronic inflammatory demylinating polyradiculoneuropathy) treatment, shows the short-term and long-term efficacy and safety of IGIV-C (intravenous immune globulin) and supports use of IGIV-C as a therapy for CIDP.”

 

  • 18262450 a double-blind placebo-controlled study at King’s College Hospital found that controlled-release oxycodone (Oxycontin®) added to gabapentin (Neurontin®) reduces diabetic neuropathic pain by a third, and improves sleep quality.

 

  • 18403272 A UC Davis double blind, placebo- controlled crossover study of neuropathic pain demonstrated analgesic response to smoking 3.5% as well as 7% cannabis (marijuana).

 

  • 18413214 Venlafaxine (Effexor®) is a combination norepinephrine-serotonin uptake inhibitor like duloxetine (Cymbalta®), the latter approved for use with peripheral neuropathy by the FDA. This study found venlafaxine to be safe, effective and well tolerated as a treatment for the pain of distal symmetrical sensorimotor polyneuropathy.

 

  • 18474189 A review of mirror visual feed back (tricking oneself into seeing the unaffected body part on the affected side of the body) as a way of decreasing neuropathic pain and normalizing movement.

 

  • 18541884 A study at Mt. Sinai Medical Center found that the application of a high concentration capsaicin dermal patch desensitized cutaneous pain receptors in HIV-associated distal sensory neuropathy.

 

  • 18600579 A discussion from the University of Toronto of fish consumption, omega-3 polyunsaturated fatty acids and docosahexaenoic acid (DHA) in the prevention and treatment of neurological disorders.

 

  • 18636234   A meta-analysis by Wake Forest University demonstrated increased functionality and chronic neuropathic pain relief from the H-Wave device manufactured by Electronic Waveform Lab.
  • 18646102 A review of the treatment of meralgia paresthetica (pain in the lateral thigh) from Charring Cross Hospital revealed over 80% response to either injection with local anesthetic/corticosteroid, or surgery; however, another study reported a 69% spontaneous recovery, without treatment.

 

  • 18646138 This Johns Hopkins review of the Cochrane Data Base of 142 studies in respect to symmetrical diabetic peripheral neuropathy “…. failed to identify a single randomized controlled trial or any well designed prospective study controlling for the non-operated limb that showed improvements in predefined points after decompressive surgery.

 

  • 18660651 A review of recent studies indicating the role of tumor necrosis factor-alpha from the injured intervertebral disc as the cause of inflammation and decreased nerve conduction velocity in sciatica, and the possibility of the tnf-alpha blocker, etanercept (Enbrel®), reversing the progression of this process.

 

  • 18673529 An Oxford study of fibromyalgia and diabetic neuropathy showed at least 50% pain reduction over 12 weeks for duloxetine (Cymbalta®) compared to placebo.

 

  • 1868812 UC Santa Barbara study of Cannabis (marijuana) for neuropathic pain.

 

  • 18774507 This Johns Hopkins review of three randomized controlled studies of 776 pregabalin (Lyrica®) and 258 controls of painful diabetic peripheral neuropathy found over four times the likelihood of at least 50% improvement with the active drug.

 

  • 18796160   An Albert Einstein College of Medicine study of painful diabetic neuropathy showing over twice the response rate for pregabalin (Lyrica®) at 49%, compared with placebo.

 

  • 18940920   A summary of studies done showing decreased pain and increased nerve regeneration in diabetic PN with acetyl-L-carnitine.

 

  • 19004197   A Guangzhou University study comparing the effectiveness of acupuncture plus acupoint-injection vs. oral carbamazepine (Tegretol®), for occipital neuralgia, with the former being more effective.
  • 19027875 A descriptive article written by E.L. Tobinick, the physician who patented a technique involving the injection of etanercept (Enbrel®) subcutaneously over the spine, thence absorbed into the cerebrospinal venous plexus, resulting in the inhibition of tumor necrosis factor, which is hypothesized to cause intervertebral disc- related pain.

 

  • 19141719 A randomized study of diabetic neuropathy patients, 89 treatment cases and 78 controls, demonstrated that silicon orthotics protected the feet from the development of painful hyperkeratotic lesions.

 

  • 19160200 Cochrane Database study of effectiveness of IVIg for CIDP

 

  • 19208243 Meta-analysis of duloxetine (Cymbalta®) vs. pregabalin (Lyrica®) for peripheral neuropathy.

 

  • 19224814 An evaluation of lidocaine (Xylocaine®) 8% spray for post-traumatic peripheral neuropathy found significant pain relief.

 

  • 19242524 Recent research has been exploring the possibility of transporting analgesic chemicals to the dorsal horn of the spinal cord, where the peripheral pain nerves enter the central nervous system. In order to transport these chemicals—enkephalin, endorphin, glutamic acid decarboxylase—rats have been infected with genetically engineered, non-replicating herpes simplex virus, which typically resides in the nerves of the dorsal horn. This complex, novel approach was reported to be safe in human trials at the 2011 meeting of the American Academy of Neurology.

 

  • 19246421 In a double blind crossover study in Taipei of botulinum toxin type A for diabetic neuropathy, there was significant improvement at 3 months post-injection.

 

  • 19252116 Mayo study of shingles prevention with anti herpes zoster vaccine

 

  • 19277838 An Italian study of CT-guided pudendal nerve block for pudendal neuralgia achieved relief of anoperineal pain, 92% at 12 months.

 

  • 19243312   A University of Leicester review of studies demonstrating prevention and amelioration of diabetic neuropathy with proinsulin C-peptide.
  • 19301378 An extensive Columbia University review of chronic demylinating polyradiculoneuropathy (CIDP), emphasized well-documented response to IVIg, plasmapheresis and corticosteroids—as well as lesser evidence supporting other agents: cyclophosphamide, rituximab, azothioprine, cyclosporine, interferon, fludarabine, mycophenolate, mofatil, and etanercept.

 

  • 19301937   A study from the University of Schleswig- Holstein comparing oral pregabalin (Lyrica®) with lidocaine (Xylocaine®) 5% medicated plaster found that the efficacy was comparable, but there were 90% fewer adverse events with the local treatment.

 

  • 19317819 A Japanese study of diabetic patients found that those with neuropathy had increased levels of vascular endothelial growth factor (VEGF), the same agent that is involved in diabetic retinopathy and wet age-related macular degeneration.

 

  • 19387178   A Johns Hopkins study of sciatica showing at least a 50% reduction in pain for the majority of patients at six months following nerve root injection with etanercept (Enbrel®).

 

  • 19406920 A study of over 5000 participants from community surveys in Singapore demonstrated that peripheral neuropathy incidence increased gradually with the level of fasting blood sugar, even at levels below the threshold for diabetes mellitus diagnosis.

 

  • 19432499 In a double-blind placebo-controlled multinational trial with post-herpetic neuralgia, improvement of pain, allodynia, quality of life and sleep was achieved with 5% lidocaine (Xylocaine®) plaster applied up to 12 hours daily.

 

  • 19499849 A Neapolitan study of 112 with carpal tunnel syndrome revealed significant improvement in symptoms and function when multivitamin controls were compared with a combination of alpha-lipoic acid 600mg. plus gamma-linolenic acid 360mg. daily.

 

  • 19555786 Chronic abdominal wall pain due to peripheral nerve impingement, often mistaken for intra-abdominal pathology, can be diagnosed by local anesthetic block of trigger points, and relieved by surgically releasing the nerve that is trapped by the muscle sheath.

 

  • 19557864 It is hypothesized that reflex sympathetic dystrophy, now known as complex regional pain syndrome (pain, hypersensitivity, sweat, edema, discoloration), may be a posttraumatic small fiber peripheral neuropathy.

 

  • 19588419 A review of the University of Oxford of 19 randomized control trials of pregabalin (Lyrica®) 600mg daily showed a minimum number of patients needed to treat (NNT), to achieve at least 50% pain relief was 5.6 for diabetic neuropathy and 5.0 for post-herpetic neuralgia.

 

  • 19590482 A study from Taiwan of carpal tunnel syndrome (wrist pain) showed no difference between those treated with corticosteroid and those receiving acupuncture.

 

  • 19655114 An extremely detailed monograph outlining possible mechanisms whereby nerve injury results in chronic pain—mediated by neuroinflammation, release of inflammatory cytokines, followed by hypersensitivity of the dorsal root ganglia, peripherally and later centrally in the dorsal horn of the spinal cord. Possible intervention using cytokine antibodies, e.g., anti- tumor necrosis factor alpha, is suggested.

 

  • 19703730 An Australian study of the local application of 10% Ketamine cream (NMDA antagonist) in patients with complex regional pain syndrome, inhibited allodynia (painful response to non-pain stimuli).

 

  • 19796802 This study at Queen’s University, Ontario, found that the antidepressant nortriptyline (Pamelor®) in combination with the anticonvulsant gabapentin (Neurontin®) controlled neuropathic pain more effectively than either medication alone.

 

  • 19801049 Under the auspices of the International Association for the Study of Pain, a consensus process developed evidence-based guidelines for the management of neuropathic pain, recommending tricyclic and dual uptake inhibitors of serotonin and norepinephrine, e.g., duloxetine (Cymbalta®), gabapentin (Neurontin®) and pregabalin (Lyrica®), and topical lidocaine (Xylocaine®) as first line treatments for neuropathic pain.

 

  • 19821395 A Cochrane database review of controlled trials of 2,220 patients prescribed duloxetine (Cymbalta®) for neuropathic pain (both neuropathy and fibromyalgia) found “moderately strong” evidence of effectiveness for doses between 60 mg. and 120 mg. daily.

 

  • 19921145 A randomized, controlled study of diabetics with varying degrees of peripheral neuropathy were given twice weekly physiotherapeutic group training in gait and balance exercises as well as function-oriented strengthening over twelve weeks. At six months there was significant improvement in balance, gait, mobility and strength

 

  • 20113411 A randomized double-blind, controlled study of post-herpetic neuralgia (shingles) comparing an 8% capsaicin dermal patch with a 0.04% control, found change in pain score of –33.8% compared to +4.9% at the end of twelve weeks.

 

  • 202236172 A double blind randomized controlled study of pregabalin (Lyrica®) 150-600 mg. daily found significant improvement in pain-related sleep interference (p < 0.001) with relief of post-traumatic peripheral neuropathic pain.

 

  • 20447305 A randomized, double blind, placebo-controlled trial of agmatine sulfate (decarboxylated amino acid arginine) 2.670 gm. daily for 14 days in cases of painful lumbar disc-associated radiculopathy, demonstrated significant improvement in pain and quality of life.

 

  • 20458651 A review of 23 studies of 5% lidocaine (Xylocaine®) medicated plaster to manage painful diabetic peripheral neuropathy, found fewer adverse events, but comparable effectiveness compared with amitriptyline (Elavil®), capsaicin, gabapentin (Neurontin®), and pregabalin (Lyrica®). 

 

  • 20460982 This article from Cook County Hospital describes paraneoplastic neurological syndrome, including peripheral neuropathy, which can occur as a result of occult cancer.

 

  • 20487567 This is a double blind randomized placebo controlled study from Louisiana State University assessing the topical oil, Neuragen PN®, in the treatment of neuropathic pain. Neuragen PN® resulted in significantly greater pain reduction (p < 0.05). 93.3% of treated patients compared to controls experienced pain relief within 30 minutes.

 

  • 20503464 An LSU study of 25 peripheral neurology patients over a 24 week course of tai chi instruction, found large improvement in plantar sensation, 6 minute walk, timed up and go, and leg strength.

 

  • 20594588 The 77 site ACCORD controlled study of Type2 diabetes found that tighter control of blood sugar (HbA1c targetimprovement in light touch and ankle jerk in those with peripheral neuropathy.

 

  • 20599049 A randomized double blind, sham-controlled study of magnetic disks applied for six weeks to the wrists of carpal tunnel syndrome patients, showed no statistically significant benefit in terms of nerve conduction or pain.

 

  • 20805210 A study from McGill University of posttraumatic or post-surgical patients with chronic neuropathic pain. A 25 mg dose of 9.4% smoked THC (marijuana) resulted in improved quality of sleep and decreased time to get to sleep. Adverse effects included cough, dry eyes, burning sensations, numbness and dizziness.

 

  • 20921842 This article discusses duloxetine (Cymbalta®) an antidepressant that blocks the reuptake of both norepinephrine and serotonin, and is approved by the FDA for treatment of peripheral neuropathy. Probable mechanism of action is the facilitation of descending pain inhibition pathways. Relief of other painful conditions, including fibromyalgia, has also been achieved.

 

  • 21127770 This article reminds us that Lyme disease, following a tick bite, and typically presenting with an expanding rash and arthritis, is a multisystem infection often causing painful neuropathies of both the cranial and peripheral nerves.

 

  • 21134121 According to a randomized controlled study of botulinum toxin (Botox®) injection for post-herpetic neuralgia (shingles), both pain and insomnia improved significantly. Opiate usage dropped 21% in the treatment group compared to the placebo group, which remained between 53-67%.

 

  • 21321947 Although previously thought to be due to thiamine deficiency, alcohol neuropathy is not reversible by vitamin B1, and, therefore, should be considered a toxic neuropathy.

 

  • 21336050 A Mayo Clinic study of transcranial magnetic stimulation of skull over the right dorsolateral prefrontal cortex of 9 subjects with refractory neuropathic pain, found that over a third had at least 50% reduction in pain. rTMS is being used more commonly for clinical depression. These patients had an average pain rating of 7.3, but no significant depression.

 

  • 21372279 A review of nine reports, 69 patients, receiving local anesthetic and corticosteroid nerve blocks for neuralgia, with 30 achieving complete pain relief, and 10 over 50% relief.

 

  • 21412914 This Cochrane Data Base review of 14 studies with 2831 patients evaluated gabapentin (Neurontin®) treatment of chronic neuropathic pain. Compared to placebo (17%), “substantial benefit” was achieved with 31%. Withdrawal from the study due to adverse event occurred in 12%.

 

  • 21719618 This study compared duloxetine (Cymbalta®) with pregabalin (Lyrica®) in the treatment of peripheral neuropathy pain in diabetics unresponsive to gabapentin (Neurontin®). Duloxetine was not statistically more effective than pregabalin. Side effects with duloxetine included insomnia, sweating, and appetite loss; pregabalin side effect was peripheral edema.

 

  • 21814197 A Mayo Clinic article reviewing therapy of chemotherapy-induced peripheral neuropathy (CIPN). The strongest evidence for prevention supports the use of intravenous calcium, magnesium and glutathione. The most effective agents for treatment appear to be serotonin/norepinephrine reuptake inhibitors.
 
  • 21998121 This is a randomized, controlled study of patients with acute sciatica. In the group treated with two subcutaneous injections of adalimubab (a tumor necrosis factor, alpha), 28% required surgery within three years, whereas 56% 0f the control group required surgery.
 
  • 21998121 This is a randomized, controlled study of patients with acute sciatica. In the group treated with two subcutaneous injections of adalimubab (a tumor necrosis factor, alpha), 28% required surgery within three years, whereas 56% of the control group required surgery.

    •  

      • 22028723 This is a case report involving the progressive addition of topical amitriptyline 5% cream, 10% ketamine cream, and DMSO 50% three times a day with reduction of pain from 26/45 to 6/25 on the McGill Pain Questionnaire.

       

      • 22082324 This article from the School of Pharmacy Practice, University of Puerto Rico, discusses what dietary supplements can be used to correct the metabolic defects that can contribute to the progression of diabetic peripheral neuropathy. Increased polyol pathway, nitric oxide deficit, increased homocysteine levels are listed as the underlying causes. Suggestions for remediation include alpha-lipoic acid, acetyl-L-carnitine, L-methyl folate, benfotiamine and pyridoxyl-6-phosphate.

       

      • 22133325 This review article presents evidence from a number of studies revealing significantly increased relief of neuropathic pain from a pairing of either gabapentin (Neurontin®) or pregabalin (Lyrica®), and an opioid, cox inhibitor, or antidepressant—greater than could be achieved with any of these agents singly.

       

      • 22028723 This is a case report involving the progressive addition of topical amitriptyline 5% cream, 10% ketamine cream, and DMSO 50% three times a day with reduction of pain from 26/45 to 6/25 on the McGill Pain Questionnaire.

       

      • 22146780 A Hamburg Medical Centre study of chemotherapy-induced peripheral neuropathy showed improvement of nerve conduction velocity in 5 out of 6 patients treated with acupuncture for 10 weeks. Although not randomized, only one patient in the control group improved.

       

      • 22307048 A review of itches that are neuropathic and not dermatologic in origin, resulting from lesions in the brain, spinal cord, and peripheral nerves. Itching due to small fiber neuropathy may respond to topical or systemically administered mexiletine (Mixitil®), local anesthetics, topical tacrolimus (Prograf®), or gabapentin (Neurontin®).

       

      • 22313580 Neuropathic pain due to peripheral nerve injury as measured by pain rating scales at three months post block, responds much better to the combination of the corticosteroid depo-methylprednisolone (Depo-Medrol®) and lidocaine (Xylocaine®) than lidocaine alone.

       

      • 22442436 A multicenter, randomized, controlled study of chronic inflammatory demyelinating polyradiculopathy (CIDP) comparing bimonthly pulses of dexamethasone (Decadron®) with eight months of daily prednisolone (Medrol®), achieving cure or long-term (4.5 year) remission in approximately a quarter of the cases.

       

      • 22480279 Of those neuropathy patients refractory to gabapentin (Neurontin®) therapy, 42.5% experienced over 50% pain reduction after switching to pregabalin (Lyrica®).

       

      • 22500483 This is an optimistic Mayo review of the use of Ketamine, an NMDA antagonist originally used as an anesthetic, that is now used as an analgesic for the management of refractory neuropathic pain, available in oral, intravenous, subcutaneous, and topical forms.

       

      • 22502623 This study of chronic herpes zoster (shingles) pain found that alternative/Chinese medicine (acupuncture, 1% procaine injections, cupping, bleeding and herbs) reduced pain on a 10-point scale at 3 weeks from 7.5 to 2.3 in the treatment group compared to 7.8 to 7.2 in the controls.

       

      • 22518362 This McGill study of neuropathic pain found that the tendency to catastrophize (exaggerate the negative outlook toward one’s illness) predicted poorer response to treatment, in this case, topical analgesia.

       

      • 22538308 A Columbia University study found over a 38% prevalence of peripheral neuropathy both in patients with celiac disease and inflammatory bowel disease, compared to 20.5% prevalence in the population (staff and visitor controls).

       

      • 22606679 Canadian Pain Society guidelines, with reservations, support the following evidence-based interventional treatments for neuropathic pain: spinal cord stimulation, intravenous infusions, epidural injections and nerve blocks. The article reviews over forty studies in this literature.

       

      • 22683276 A randomized controlled study of topical 0.1% clonidine (Catapress®) gel with painful diabetic neuropathy, found significant reduction in the level of foot pain among those patients who were pain-sensitive to capsaicin.

       

      • 22696371 Diabetic neuropathy affects 10% of diabetics at diagnosis, and 40-50% after 10 years. A Cochrane database review of 17 studies showed that enhanced control of blood sugar resulted in reduced nerve conduction and vibration threshold abnormalities in Type I diabetes mellitus.

       

      • 22701355 This paper discusses the experimental use of transplanted bone marrow derived cells as a source of cultured Schwann Cells that can be used with conduits to induce nerve grafts to repair injured peripheral nerves.
      •  22050401 This Kuwaiti study found that those Type 2 diabetics with peripheral neuropathy had significantly lower vitamin D levels than those without. Further study assessing vitamin D as a preventive is suggested.