Neurochemical research
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Neurochemical research · Oct 2008
Mu-opioid receptor in the nucleus submedius: involvement in opioid-induced inhibition of mirror-image allodynia in a rat model of neuropathic pain.
The current study investigated the roles of various subtypes of opioid receptors expressed in the thalamic nucleus submedius (Sm) in inhibition of mirror-image allodynia induced by L5/L6 spinal nerve ligation in rats. Morphine was microinjected into the Sm, which produced a dose-dependent inhibition of mirror-image allodynia; this effect was antagonized by pretreatment with non-selective opioid receptor antagonist naloxone. ⋯ The kappa-receptor agonist, spiradoline mesylate salt, failed to alter the mirror-image allodynia. These results suggest that Sm opioid receptor signaling is involved in inhibition of mirror-image allodynia; this effect is mediated by mu- (but not delta- and kappa-) opioid receptors in the rat model of neuropathic pain.
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Neurochemical research · Oct 2008
ReviewIntracellular signaling in primary sensory neurons and persistent pain.
During evolution, living organisms develop a specialized apparatus called nociceptors to sense their environment and avoid hazardous situations. Intense stimulation of high threshold C- and Adelta-fibers of nociceptive primary sensory neurons will elicit pain, which is acute and protective under normal conditions. A further evolution of the early pain system results in the development of nociceptor sensitization under injury or disease conditions, leading to enhanced pain states. ⋯ Inflammatory mediators such as proinflammatory cytokines (TNF-alpha, IL-1beta), PGE(2), bradykinin, and NGF increase the sensitivity and excitability of nociceptors by enhancing the activity of pronociceptive receptors and ion channels (e.g., TRPV1 and Na(v)1.8). We will review the evidence demonstrating that activation of multiple intracellular signal pathways such as MAPK pathways in primary sensory neurons results in the induction and maintenance of peripheral sensitization and produces persistent pain. Targeting the critical signaling pathways in the periphery will tackle pain at the source.
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Neurochemical research · Oct 2008
ReviewCharacteristics of HCN channels and their participation in neuropathic pain.
Neuropathic pain is induced by the injury to nervous systems and characterized by hyperalgesia, allodynia and spontaneous pain. The underlying mechanisms include peripheral and central sensitization resulted from neuronal hyperexcitability. ⋯ We overview its biophysical properties, physiological functions, followed by focusing on the current progress in the study of its role in the development of neuropathic pain. We attempt to provide a comprehensive review of the potential valuable target, HCN channels, in the treatment of neuropathic pain.
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Neurochemical research · Oct 2008
Behavioral and electrophysiological evidence for the differential functions of TRPV1 at early and late stages of chronic inflammatory nociception in rats.
We previously reported that vanilloid receptor type 1 (VR1, or TRPV1) was up-regulated in dorsal root ganglion (DRG) and the spinal dorsal horn after chronic inflammatory pain produced by complete Freund's adjuvant (CFA) injection into the plantar of rat hind paw. In the present study, we found that subcutaneous or intrathecal application of capsazepine (CPZ), a TRPV1 competitive antagonist, could inhibit thermal hyperalgesia on day 1 and on day 14 but not on day 28 after CFA injection. ⋯ Under radiant heat stimulation to the receptive field skin, subcutaneous application of CPZ significantly inhibited the background activity and extended the response latency of WDR neurons on day 14. These results provide new evidence for the functional significance of TRPV1 at the early stage, but not the late stage, in the rat model of CFA-induced inflammatory pain.
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Neurochemical research · Oct 2008
Involvement of spinal somatostatin receptor SST(2A) in inflammation-induced thermal hyperalgesia: ultrastructural and behavioral studies in rats.
Our previous results have shown that somatostatin receptor subtype SST(2A) is responsible for thermal, but not mechanical nociceptive transmission in the rat spinal cord. The present study was undertaken to further examine the ultrastructural localization of SST(2A) receptor in lamina II of the spinal dorsal horn and the role of SST(2A) receptor in thermal hyperalgesia following Complete Freund's Adjuvant (CFA)-induced inflammation. We found that SST(2A) receptors in lamina II are located primarily in postsynaptic dendrites and soma, but not in axons or synaptic terminals. ⋯ Intrathecal application of SST(2A) agonist SOM-14 at different doses prior to CFA treatment did not influence thermal hyperalgesia in inflamed rats, but at a low dose shortened PWL evoked by noxious heating in normal rats. These results suggest that spinal SST(2A) receptors play a key role in triggering the generation, but not maintenance, of thermal hyperalgesia evoked by CFA-induced inflammation. The up-regulation of SST(2A) receptors in the spinal cord may be one of the mechanisms underlying inflammation-induced thermal hyperalgesia.