Articles: hyperalgesia.
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Pro-inflammatory cytokine high mobility group box-1 (HMGB-1) is involved in inflammation in the central nervous system, but less is known about its biological effects in the peripheral nervous system. In the present study, the role of HMGB-1 in the primary afferent nerve was investigated in the context of the pathophysiology of peripheral nerve injury-induced pain hypersensitivity. Real-time PCR confirmed an increase in HMGB-1 mRNA expression in the dorsal root ganglion (DRG) and spinal nerve at 1 day after spinal nerve ligation (SNL). ⋯ Receptor for advanced glycation end products (RAGE), one of the major receptors for HMGB-1, was expressed in the primary afferent neurons and SGCs in the DRG, as well as in Schwann cells in the spinal nerve. These results indicate that HMGB-1 is synthesized and secreted into the DRG and spinal nerve, and contributes to the development of neuropathic pain after nerve injury. Blocking HMGB-1/RAGE signalling might thus be a promising therapeutic strategy for the management of neuropathic pain.
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The involvement of the 5-HT(7) receptor in nociception and pain, particularly chronic pain (i.e., neuropathic pain), has been poorly investigated. In the present study, we examined whether the 5-HT(7) receptor participates in some modulatory control of nerve injury-evoked mechanical hypersensitivity and thermal (heat) hyperalgesia in mice. Activation of 5-HT(7) receptors by systemic administration of the selective 5-HT(7) receptor agonist AS-19 (1 and 10mg/kg) exerted a clear-cut reduction of mechanical and thermal hypersensitivities that were reversed by co-administering the selective 5-HT(7) receptor antagonist SB-258719. ⋯ The 5-HT(7) receptor co-localized with GABAergic cells in the dorsal horn of the spinal cord, suggesting that the activation of spinal inhibitory GABAergic interneurons could contribute to the analgesic effects of 5-HT(7) receptor agonists. In addition, a significant increase of 5-HT(7) receptors was found by immunohistochemistry in the ipsilateral dorsal horn of the spinal cord after nerve injury, suggesting a "pain"-triggered regulation of receptor expression. These results support the idea that the 5-HT(7) receptor subtype is involved in the control of pain and point to a new potential use of 5-HT(7) receptor agonists for the treatment of neuropathic pain.
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We investigated antinociceptive activity of botulinum toxin type A (BTX-A) in a model of diabetic neuropathic pain in rats. Male Wistar rats were made diabetic by a single intraperitoneal injection of streptozotocin (80mg/kg). Sensitivity to mechanical and thermal stimuli was measured with the paw-pressure and hot-plate test, respectively. ⋯ When applied intrathecally, BTX-A (1U/kg) reduced diabetic hyperalgesia within 24h supporting the assumption of retrograde axonal transport of BTX-A from the peripheral site of injection to central nervous system. The results presented here demonstrate the long-lasting pain reduction after single BTX-A injection in the animals with diabetic neuropathy. The bilateral pain reduction after unilateral toxin application and the effectiveness of lower dose with the faster onset after the intrathecal injection suggest the involvement of the central nervous system in the antinociceptive action of BTX-A in painful diabetic neuropathy.
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Non-invasive, movement-based models were used to investigate muscle pain. In rats, the masseter muscle was rapidly stretched or electrically stimulated during forced lengthening to produce eccentric muscle contractions (EC). Both EC and stretching disrupted scattered myofibers and produced intramuscular plasma extravasation. ⋯ In contrast, stretching significantly increased the number of P2X(3) muscle afferent neurons for 12d. The sustained, elevated P2X(3) expression evoked by EC and stretching may enhance nociceptor responsiveness to ATP released during subsequent myofiber damage. Movement-based actions such as EC and muscle stretching produce unique tissue responses and modulate neuropeptide and nociceptive receptor expression in a manner particularly relevant to repeated muscle damage.
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The primary aim of the present study was to investigate whether there is a relationship between central hypersensitivity (assessed by pressure pain thresholds of uninjured tissues) and intradiscal pain threshold during discography. The secondary aim was to test the hypothesis that peripheral noxious stimulation dynamically modulates central hypersensitivity. ⋯ Central hypersensitivity may influence intradiscal pain threshold, but with a modest quantitative impact. The diagnostic value of provocation discography is therefore not substantially impaired. Regional, but not generalized central hypersensitivity is dynamically modulated by ongoing peripheral nociceptive input.