Articles: neuralgia.
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Nicotinic receptors in the central nervous system (nAChRs) are known to play important roles in pain processing and modulate behavioral responses to analgesic drugs, including nicotine. The presence of the α5-neuronal nicotinic accessory subunit in the nicotinic receptor complex is increasingly understood to modulate reward and aversive states, addiction, and possibly pathological pain. In the current study, using α5-knockout (KO) mice and subunit-specific antibodies, we assess the role of α5-containing neuronal nicotinic receptors in neuropathic pain and in the analgesic response to nicotine. ⋯ Nevertheless, thermal analgesic response to nicotine was marginally reduced in CCI α5-KO mice at 4 days after CCI, but not at later timepoints or after PSNL. Interestingly, upon daily intermittent nicotine injections in unoperated mice, WT animals developed tolerance to nicotine-induced analgesia to a larger extent than α5-KO mice. Our results suggest that α5-containing nAChRs mediate analgesic tolerance to nicotine but do not play a major role in neuropathic pain.
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Activated mammalian target of rapamycin (P-mTOR) has been shown to maintain the sensitivity of subsets of small-diameter primary afferent A-nociceptors. Local or systemic inhibition of the mTOR complex 1 (mTORC1) pathway reduced punctate mechanical and cold sensitivity in neuropathic pain and therefore offered a new approach to chronic pain control. In this study, we have investigated the effects of the rapamycin analog temsirolimus (CCI-779) on itch. ⋯ We also examined the colocalization of P-mTOR with gastrin-releasing peptide, a putative marker for some itch-sensitive primary afferents, and found that P-mTOR was coexpressed in less than 5% of gastrin-releasing peptide-positive fibers in the mouse skin. Taken together, the data highlight the role that P-mTOR-positive A-fibers play in itch signaling and underline the importance of the mTORC1 pathway in the regulation of homeostatic primary afferent functions such as pain and itch. The actions of the antidiabetic drug metformin in ameliorating nonhistamine-mediated itch also suggest a new therapeutic route for the control of this category of pruritus.
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Neuropathic pain is a common complication of treatment with the anti-neoplastic drug paclitaxel. Animal studies suggest neuroinflammation and transient receptor potential channels TRPA1 and TRPV4 are involved in the pathogenesis of pain in this condition. However, how neuroinflammation and TRPA1 and TRPV4 are linked to cause pain in paclitaxel-treated animals is not known. ⋯ These results suggest that paclitaxel activation of TLR-4 to cause release of TNF-α from satellite glial cells increases the expression of TRPA1 and TRPV4 in DRG neurons to cause neuropathic pain.
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Am J Phys Med Rehabil · Aug 2015
Case ReportsCapsaicin 8% Patch for Central and Peripheral Neuropathic Pain of Persons with Incomplete Spinal Cord Injury: Two Case Reports.
Neuropathic pain after spinal cord injury is common and often refractory to standard treatments. The capsaicin 8% patch is a Food and Drug Administration-approved treatment of neuropathic pain in postherpetic neuralgia and has demonstrated significant efficacy in human immunodeficiency virus-autonomic neuropathy. The patch defunctionalizes transient receptor potential vanilloid 1 receptors, impairing cutaneous nociceptors for a prolonged period (i.e., 8-12 wks) with no systemic side effects. ⋯ Average onset of relief of 4 days and average duration of relief of 197 days, requiring only one to four applications per year, paralleled findings reported in postherpetic neuralgia and human immunodeficiency virus-autonomic neuropathy trials. Upregulation of capsaicin-sensitive transient receptor potential vanilloid 1 receptors after spinal cord injury has been reported. The capsaicin 8% patch is a promising therapeutic agent for neuropathic pain in spinal cord injury.
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Randomized Controlled Trial
Combination of morphine with nortriptyline for neuropathic pain.
First-line neuropathic pain drugs, including tricyclic antidepressants, are not always effective, and opioids have been recommended as second line. This trial evaluates a nortriptyline-morphine combination, compared with each monotherapy. In this randomized, double-blind crossover trial, patients with neuropathic pain were enrolled at 1 site between January 25, 2010, and May 22, 2014, and randomized in a 1:1:1 ratio using a balanced Latin square design to receive oral nortriptyline, morphine, and their combination. ⋯ Combination treatment resulted in moderate-severe constipation in 43% vs 46% with morphine (P = 0.82) and 5% with nortriptyline (P < 0.0001). Combination treatment resulted in moderate-severe dry mouth in 58% vs 49% with nortriptyline (P = 0.84) and 13% with morphine (P < 0.0001). This trial suggests superior efficacy of a nortriptyline-morphine combination over either monotherapy with constipation, dry mouth, and somnolence as the most frequent adverse effects.