Treatment Of Painful Peripheral Neuropathy Research Articles

Immunoglobulin Use for the Management of Painful Peripheral Neuropathy: A Systematic Review and Meta-Analysis.

Immunoglobulins (IG) are widely used for the treatment of a variety of immune-mediated diseases. The exact mechanism of action remains unknown, but IG modulate the expression and function of Fc receptors, interfere with complement activation and production of cytokines, neutralize pathogenic autoantibodies, and affect the activation and effector functions of B and T lymphocytes. Immunoglobulins are usually delivered intravenously, and are effective in ameliorating motor symptoms, and/or preventing disease progression in immune-mediated neuropathies, including Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy. The aim of this systematic review and meta-analysis was to study the potential of IG for the treatment of painful peripheral neuropathy (PPN). The outcome of interest was the percentage of patients with PPN who achieved pain relief following IG administration. We performed a systematic literature search on March 17, 2022, in the PubMed database without any publication date restrictions. We also looked for unpublished or ongoing trials in clinicaltrials.org. Pain reduction following IG treatment had to be within the aims (primary or secondary). The aforementioned literature search strategy revealed five studies (two open-label, three randomized placebo-controlled) eligible to be included. The pooled estimate of the percentage of patients with PPN who received immunoglobulins and reported pain relief was found to be 65% (95% CI 58-71%). The likelihood of achieving pain relief with immunoglobulin treatment was 2.9 times higher (95% CI 1.6-5.2) compared to placebo (p = 0.0003). The use of IG for the treatment of pain due to peripheral neuropathy has a potential therapeutic benefit. Further studies across patients with different types of painful peripheral neuropathy are needed to better characterize this effect. Registration number on PROSPERO: CRD42022319614.

B12 as a Treatment for Peripheral Neuropathic Pain: A Systematic Review.

Neuropathic pain describes a range of unpleasant sensations caused by a lesion or disease of the somatosensory nervous system. The sensations caused by neuropathic pain are debilitating and improved treatment regimens are sought in order to improve the quality of life of patients. One proposed treatment for neuropathic pain is vitamin B12, which is thought to alleviate pain by a number of mechanisms including promoting myelination, increasing nerve regeneration and decreasing ectopic nerve firing. In this paper, the evidence for B12 as a drug treatment for neuropathic pain is reviewed. Twenty four published articles were eligible for inclusion in this systematic review in which a range of treatment regimens were evaluated including both B12 monotherapy and B12 in combination with other vitamins or conventional treatments, such as gabapentinoids. Overall, this systematic review demonstrates that there is currently some evidence for the therapeutic effect of B12 in the treatment of post-herpetic neuralgia (level II evidence) and the treatment of painful peripheral neuropathy (level III evidence).

Complementary and Alternative Medicine for Painful Peripheral Neuropathy

The purpose of our manuscript is to review the current evidence supporting the use of complementary and alternative medicine (CAM) in neuromuscular disease, specifically in painful peripheral neuropathy (PPN). We outline the therapeutic challenges of this debilitating condition and describe the best evidence for incorporating such therapies into clinical practice. The most studied modalities include lifestyle modifications with diet and exercise, supplements, and acupuncture. CAM therapies such as yoga, meditation, electrical stimulation, neuromodulatory devices, and cannabis are mentioned as emerging therapies. Current data suggests that targeted lifestyle modifications, including aerobic exercise and diet modifications that promote weight loss, may improve the natural course of diabetic painful neuropathy and potentially other types of neuropathy. A number of studied dietary supplements and vitamins including B vitamins, vitamin D, alpha-lipoic acid, and acetyl-L-carnitine improve both subjective and objective neuropathic measures. A wide range of neuromodulatory devices and electrical stimulation modalities demonstrate mixed results, and further studies are needed to confirm their benefit. Finally, acupuncture and yoga both demonstrate benefit in a variety of PPNs. Multiple CAM therapies show efficacy in the treatment of PPN. From the strongest level of evidence to the least, lifestyle modifications including exercise and diet; supplements including B12, alpha lipoic acid, acetyl-L-carnitine, and vitamin D in deficient patients; followed by acupuncture and yoga may alleviate symptoms of PPN.

Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia

Duloxetine is a balanced serotonin and noradrenaline reuptake inhibitor licensed for the treatment of major depressive disorders, urinary stress incontinence and the management of neuropathic pain associated with diabetic peripheral neuropathy. A number of trials have been conducted to investigate the use of duloxetine in neuropathic and nociceptive painful conditions. This is the first update of a review first published in 2010. To assess the benefits and harms of duloxetine for treating painful neuropathy and different types of chronic pain. On 19th November 2013, we searched The Cochrane Neuromuscular Group Specialized Register, CENTRAL, DARE, HTA, NHSEED, MEDLINE, and EMBASE. We searched ClinicalTrials.gov for ongoing trials in April 2013. We also searched the reference lists of identified publications for trials of duloxetine for the treatment of painful peripheral neuropathy or chronic pain. We selected all randomised or quasi-randomised trials of any formulation of duloxetine, used for the treatment of painful peripheral neuropathy or chronic pain in adults. We used standard methodological procedures expected by The Cochrane Collaboration. We identified 18 trials, which included 6407 participants. We found 12 of these studies in the literature search for this update. Eight studies included a total of 2728 participants with painful diabetic neuropathy and six studies involved 2249 participants with fibromyalgia. Three studies included participants with depression and painful physical symptoms and one included participants with central neuropathic pain. Studies were mostly at low risk of bias, although significant drop outs, imputation methods and almost every study being performed or sponsored by the drug manufacturer add to the risk of bias in some domains. Duloxetine at 60 mg daily is effective in treating painful diabetic peripheral neuropathy in the short term, with a risk ratio (RR) for ≥ 50% pain reduction at 12 weeks of 1.73 (95% CI 1.44 to 2.08). The related NNTB is 5 (95% CI 4 to 7). Duloxetine at 60 mg daily is also effective for fibromyalgia over 12 weeks (RR for ≥ 50% reduction in pain 1.57, 95% CI 1.20 to 2.06; NNTB 8, 95% CI 4 to 21) and over 28 weeks (RR 1.58, 95% CI 1.10 to 2.27) as well as for painful physical symptoms in depression (RR 1.37, 95% CI 1.19 to 1.59; NNTB 8, 95% CI 5 to 14). There was no effect on central neuropathic pain in a single, small, high quality trial. In all conditions, adverse events were common in both treatment and placebo arms but more common in the treatment arm, with a dose-dependent effect. Most adverse effects were minor, but 16% of participants stopped the drug due to adverse effects. Serious adverse events were rare. There is adequate amounts of moderate quality evidence from eight studies performed by the manufacturers of duloxetine that doses of 60 mg and 120 mg daily are efficacious for treating pain in diabetic peripheral neuropathy but lower daily doses are not. Further trials are not required. In fibromyalgia, there is lower quality evidence that duloxetine is effective at similar doses to those used in diabetic peripheral neuropathy and with a similar magnitude of effect. The effect in fibromyalgia may be achieved through a greater improvement in mental symptoms than in somatic physical pain. There is low to moderate quality evidence that pain relief is also achieved in pain associated with depressive symptoms, but the NNTB of 8 in fibromyalgia and depression is not an indication of substantial efficacy. More trials (preferably independent investigator led studies) in these indications are required to reach an optimal information size to make convincing determinations of efficacy.Minor side effects are common and more common with duloxetine 60 mg and particularly with 120 mg daily, than 20 mg daily, but serious side effects are rare.Improved direct comparisons of duloxetine with other antidepressants and with other drugs, such as pregabalin, that have already been shown to be efficacious in neuropathic pain would be appropriate. Unbiased economic comparisons would further help decision making, but no high quality study includes economic data.

Potential for ocular irritation from topical mepivacaine gel and cream dosage forms

Mepivacaine gel and cream formulations are being investigated for topical application to the skin for the treatment of painful peripheral neuropathy. Although such formulations are not intended for application to the eye, there is potential for inadvertent contact with the eye. This study evaluated the ocular irritancy potential of six mepivacaine formulations in the rabbit. There were twelve groups in the study. All groups received active test article (mepivacaine gel or cream) into the right eye. Among the twelve groups, six received no treatment into the left eye, thereby serving as untreated controls. The remaining six groups received test article devoid of active drug into the left eye, thereby serving as vehicle controls. Animals were physically immobilized and the dosage form applied as a single 100 mg dose into the conjunctival sac. The rabbit was then released. The ocular response after each active test article application was compared with corresponding vehicle control or untreated control in the contralateral eye. Corneal and iris lesions, conjunctival redness and chemosis were recorded at 1, 24, 48 and 72 hours. The total ocular lesion score (sum of all scores) was derived at each timepoint. There were no evident toxic systemic symptoms observed in the animals during observation period. All animals survived until study completion. The instillation of 100 mg of mepivacaine containing gel or cream into the rabbit eye did not produce any significant or long lasting ocular changes. However, mild to moderate, early-onset and transient ocular changes such as conjunctival hyperemia, chemosis, iritis and corneal opacities were seen in a few animals at some time points over the 72 hour observation periods. Based on current European Union guidelines, the tested mepivacaine dosages may be considered to be “not irritating” to the rabbit eye. Supported by a grant from TheraQuest Biosciences, Inc.

Treatment of Painful Peripheral Neuropathy

Treatment of neuropathic pain is the primary focus of management for many patients with painful peripheral neuropathies. Antidepressants and anticonvulsants are the two medication classes most widely studied and represent first-line agents in the management of neuropathic pain. The number of pharmacologic agents and interventional procedures that have shown effectiveness in the treatment of neuropathic pain continues to expand. Pain management should begin with a concerted effort to identify the etiology of the neuropathy, because directed therapy can help alleviate the symptoms. When initiating pharmacotherapy for neuropathic pain, one must individualize treatment and choose an agent that is likely to be tolerated, because adverse events are common for many of these agents. Neuropathic pain management remains challenging because of heterogeneous responses between individuals and the fact that pain relief is rarely complete. However, monotherapy with a well-chosen agent or rational polypharmacy that combines medications with different mechanisms of action will benefit a majority of patients with neuropathic pain.

Selective Nerve Root Stimulation (SNRS) in the Treatment of End-Stage, Diabetic, Peripheral Neuropathy: A Case Report

Spinal cord stimulation (SCS) for the treatment of painful peripheral neuropathy (PN) has been met with mixed results. It has been suggested that early-stage symptoms that are sympathetically maintained (SMP) are more likely to respond to SCS, while progressive sympathetically independent symptoms (SIP) will not. Peripheral nerve stimulation (PNS), however, has successfully treated certain SIP presentations. With the advent of new selective nerve root stimulation (SNRS) strategies, the possibility of utilizing epidural, peripheral neurostimulation was investigated in a patient with endstage, diabetic, "dying back" peripheral SIP.

Capsaicin blocks tetrodotoxin-resistant sodium potentials and calcium potentials in unmyelinated C fibres of biopsied human sural nerve in vitro

Topical application of capsaicin has been tested recently for treatment of painful peripheral neuropathy. In the present study, effects of capsaicin were explored on compound action potentials of isolated fascicles from human sural nerve biopsies. Capsaicin reduced the C fibre component by 30–60%; the remaining C fibres were not sensitive to the drug. A good correlation was found between the sensitivity of C fibres to capsaicin and their resistance to tetrodotoxin (TTX), i.e. C fibre action potentials recorded in the presence of TTX were completely blocked by capsaicin. Calcium action potentials seen after inhibition of axonal potassium conductances were also completely suppressed. The data indicate that application of capsaicin nearby human peripheral nerves might prevent action potential conduction in specific subtypes of C fibres.