Articles: neuralgia.
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Advances in therapy · May 2020
ReviewPostherpetic Neuralgia: Current Evidence on the Topical Film-Forming Spray with Bupivacaine Hydrochloride and a Review of Available Treatment Strategies.
This is a comprehensive review of the literature about the use of bupivacaine hydrochloride for the treatment of post-herpetic neuralgia (PHN). It briefly reviews the background, biology, diagnosis and conventional treatment for PHN, and then introduces and compares the recent evidence for the use of topical bupivacaine. ⋯ PHN is defined by pain lasting 90 days or more after the initial presentation of herpes zoster ("Shingles", HZ) rash and is the most common complication of this disease. A product of re-activation of the Varicella-Zoster virus (VZV), HZ is diagnosed more than 1 million times annually in the United States. Approximately 20% of patients with HZ will experience PHN and will continue to suffer intermittent neuropathic symptoms, including itching and pain, that is sharp, stabbing, throbbing or burning, with the pain localized to the site of their original rash. This long-lasting pain compares with the severity of long-standing rheumatics and osteo-arthritis and is accompanied by severe allodynia causing significant suffering, and a financial burden that is manifested in both healthcare costs and loss of quality-adjusted life years. Prevention of PHN may be achieved with the Zoster vaccine, although there is still a large segment of unvaccinated population. Moreover, the Zoster vaccine is not always effective for prevention. Current treatment includes medical (systemic tricyclic antidepressants, anticonvulsants and opioids, topical lidocaine and capsaicin) and interventional (subcutaneous Botox injections, nerve blocks and nerve stimulation) therapies. These therapies are not always effective, and each carries their own profile of side effects and risks. Moreover, up to 50% of patients with PHN are refractory to management. Recent evidence is emerging to support the use of topical local anesthetics for the treatment of PHN. Two small studies recently found topical lidocaine spray to be effective in treating paroxysmal pain attacks associated with PHN. Bupivacaine is a longer-lasting local anesthetic, and a film-forming formulation allows easy and durable application to the affected skin. Recent studies show that topical film-forming bupivacaine is safe and as effective as lidocaine for the treatment of PHN. PHN is an important though common complication of HZ and can cause long-lasting pain and disability. Current treatment for PNH is limited by efficacy and safety profiles of individual therapies. Recent evidence points to topical local anesthetics as an effective and safe alternative to conventional therapy. Film-forming bupivacaine may offer a durable and safe option for this otherwise difficult to treat syndrome.
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Experimental neurology · May 2020
Upregulation of transcription factor 4 downregulates NaV1.8 expression in DRG neurons and prevents the development of rat inflammatory and neuropathic hypersensitivity.
The voltage sodium channel 1.8 (NaV1.8) in the dorsal root ganglion (DRG) neurons contributes to the initiation and development of chronic inflammatory and neuropathic pain. However, an effective intervention on NaV1.8 remains to be studied in pre-clinical research and clinical trials. In this study, we aimed to investigate whether transcription factor 4 (TCF4) overexpression represses NaV1.8 expression in DRG neurons, thus preventing the development of chronic pain. ⋯ We showed that the intrathecal delivery of TCF4 overexpression virus significantly repressed the increase of NaV1.8 and prevented the development of hyperalgesia in rats. Moreover, we confirmed the efficient role of an overexpressed TCF4 in preventing the CFA- and SNI-induced neuronal hyperexcitability by calcium imaging. Our results suggest that attenuating the dysregulation of NaV1.8 by targeting TCF4 may be a novel therapeutic strategy for chronic inflammatory and neuropathic pain.
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Neuropathic pain is a debilitating status that is insusceptible to the existing analgesics. It is important to explore the underlying pathophysiological changes and search for new pharmacological approaches. Transient receptor potential canonical 6 (TRPC6) is a mechanosensitive channel that is expressed by dorsal root ganglia and glial cells. It has been demonstrated that this channel in dorsal root ganglia plays essential roles in the formation of mechanical hyperalgesia in neuropathic pain. Recent pharmacological screening suggests that larixyl acetate (LA), a main constituent of larch resin, is able to selectively inhibit TRPC6 function. But whether LA is effective in treating neuropathic pain remains unknown. We investigated the efficacy of LA in rat neuropathic pain model, examined its effects on central neuroinflammation, and explored the possible molecular mechanisms by targeting the spinal dorsal horn. ⋯ These data demonstrate that i.t. applied LA exhibits analgesic and anti-inflammatory action in neuropathic pain. The action of LA involves the suppression of TRPC6 and p38 signaling in the microglia. LA may be thus a promising pharmacological candidate for the treatment of intractable chronic pain.