Pain
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Cannabinoids act at receptors on peripheral and central neurons to modulate diverse physiological functions and produce analgesia. Corneal sensory nerves express the CB1 cannabinoid receptor and project to two spatially discrete regions of the lower brainstem, the trigeminal interpolaris/caudalis (Vi/Vc) transition and subnucleus caudalis/upper cervical cord (Vc/C1) junction region. The function of CB1 expression on corneal nerves is not known. ⋯ These results indicated that cannabinoid receptor agonists acted, at least in part, at CB1 receptors in the anterior eye to reduce corneal stimulation-evoked trigeminal brainstem neural activity. Corneal nociceptor-evoked activity at the Vi/Vc transition was reduced significantly by topical WIN-2, while activity at the Vc/C1 junction region displayed only minor decreases. These findings were consistent with the hypothesis that CB1 receptors affect the activity of corneal-responsive neurons that preferentially contribute to homeostasis of the anterior eye and/or reflexive aspects of nociception rather than the sensory-discriminative aspects of corneal nociception.
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This study was designed to determine whether intrathecal octreotide (sandostatin), a synthetic octapeptide derivative of somatostatin, relieved thermal hyperalgesia and reduced the evoked spinal c-Fos expression in rats with chronic constriction injury (CCI) of the sciatic nerve. Intrathecal catheters were implanted in rats 7 days before CCI of the sciatic nerve over the left hind limb. After confirmation of the development of thermal hyperalgesia by decreased paw withdrawal latencies (PWL) to heat stimulation 7 days after CCI, intrathecal sandostatin at 20, 40, and 80 microg was administered, respectively. ⋯ Expression of Fos-LI neurons in the 80 microg group was nearly completely inhibited. These data suggest that intrathecal sandostatin significantly relieved thermal hyperalgesia behaviorally but with limited effects and dose-dependently reduced spinal Fos-LI neurons expression evoked by stroking stimulation, which may reflect mechanical allodynia in rats with sciatic constriction injury. This implies that intrathecal sandostatin was effective in the treatment of neuropathic pain.
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The interaction between electroacupuncture and an N-methyl-D-aspartic acid (NMDA) receptor antagonist, (DL-2-amino-5-phosphonopentanoic acid; AP5), or an (+/-)-alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainite (AMPA/KA) receptor antagonist, (6,7-dinitroquinoxaline-2,3 (1H,4H); DNQX) administered intrathecally on carrageenan-induced thermal hyperalgesia and spinal c-Fos expression was investigated. The latency of paw withdrawal (PWL) from a thermal stimulus was used as a measure of hyperalgesia in awake rats. Intrathecal (i.t.) injection of 1 and 10 nmol AP5, but not DNQX, markedly increased the PWL of the carrageenan-injected paw. ⋯ When a combination of electroacupuncture with 10 nmol AP5 or 100 nmol DNQX was used, the level of Fos expression in the spinal cord induced by carrageenan was significantly lower than electroacupuncture or i.t. injection of AP5 or DNQX alone. These results demonstrate that electroacupuncture and NMDA or AMPA/KA receptor antagonists have a synergetic anti-nociceptive action against inflammatory pain. Furthermore, this study supports the idea that both NMDA and AMPA/KA receptors are involved in spinal nociceptive transmission in carrageenan-inflamed rats, with the former more preferentially mediating transmission of nociceptive information from cutaneous tissue.