Journal of pharmacological sciences
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Arginine vasopressin (AVP) receptors have been classified into V1a, V1b, and V2 subtypes. Recent studies have demonstrated the involvement of AVP in anti-nociception and in morphine-induced anti-nociception. ⋯ Here, we have summarized the role of V1-receptor subtypes in behavioral responses to noxious stimuli and to morphine. In this review, we focus on studies using mice lacking the V1a receptor (V1a(-/-) mice) and the V1b receptor (V1b(-/-) mice).
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Accumulating evidence indicates a pivotal role for neuroinflammation in ischemic and excitotoxic brain injury. Cytokine-induced neutrophil chemoattractant-1 (CINC-1) is a CXC chemokine implicated in the infiltration of inflammatory cells into the brain parenchyma. In this study, we investigated the effect of N-methyl-D-aspartate (NMDA)-induced neuronal injury on CINC-1 production in the organotypic cortico-striatal slice cultures. ⋯ NMDA-induced CINC-1 mRNA expression was significantly inhibited by U0126, a mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor. These results suggest that NMDA-evoked neuronal injury induced astrocytic CINC-1 production via a MEK/ERK signaling pathway. Manipulation of this signaling pathway may serve as a target for suppressing neuroinflammation and, thereby, treating ischemic brain injury.
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The present study was undertaken to clarify how spinal muscarinic receptors are involved in the antinociceptive effects in thermal stimulation. Intrathecal (i.t.) injection of the muscarinic agonist McN-A-343 inhibited the tail-flick response to noxious thermal stimulation in a dose-dependent manner (31.5 - 63.0 nmol). This McN-A-343-induced antinociceptive effect was dose-dependently inhibited by intrathecal (i.t.) injection of a nonselective muscarinic receptor antagonist atropine, the selective muscarinic M(1) antagonist pirenzepine, or the M(4) antagonist himbacine. ⋯ In contrast, the selective muscarinic M(2) antagonist methoctramine did not inhibit the antinociceptive effects of McN-A-343. In addition, the McN-A-343-induced antinociceptive effect was attenuated by i.t. injection of the GABA(A) antagonist bicuculline, but not by injection of the GABA(B) antagonist CGP35348. These results suggest that McN-A-343 produces its antinociceptive effect on the response to thermal stimulation via spinal muscarinic M(1) receptors and, at least in part, through neuronal pathways involving spinal GABA(A) receptors in mice.
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Comparative Study
Pharmacological differences between static and dynamic allodynia in mice with herpetic or postherpetic pain.
In the present study, we investigated whether dynamic and static allodynia would be developed in the affected dermatome in murine models of herpetic pain and postherpetic neuralgia and pharmacologically characterized the allodynia. Inoculation with herpes simplex virus type-1 on the femur induced skin lesions in the dermatome including the plantar region of the hind paw from day 5 to day 21 after inoculation. Dynamic allodynia became apparent in the hind paw from day 3 to at least day 42. ⋯ Gabapentin (30 mg/kg, p.o.) markedly inhibited both static and dynamic allodynia. Developmental and pharmacological differences between static and dynamic allodynia suggest that independent mechanisms are responsible for dynamic and static allodynia. This murine model may be useful for the study of the mechanisms of dynamic allodynia of herpetic pain or postherpetic neuralgia and the development of new analgesics effective against the dynamic allodynia.
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To clarify the role of peroxisome proliferator activated receptor gamma (PPARgamma) in neuropathic pain, we examined the effect of pioglitazone, a PPARgamma agonist, on tactile allodynia and thermal hyperalgesia in a neuropathic pain model. Mice were subjected to partial sciatic nerve ligation (PSL) and given pioglitazone (1 - 25 mg/kg, p.o.) once daily. PPARgamma was distributed in the neurons of the dorsal root ganglion and the dorsal horn of the spinal cord and in the adipocytes at the epineurium of the sciatic nerve in naive mice. ⋯ A single administration of pioglitazone to mice on day 7 of PSL did not alter tactile allodynia and thermal hyperalgesia. PSL-induced upregulation of tumor necrosis factor-alpha and interleukin-6, which are essential for neuropathic pain, was suppressed by pioglitazone for the first week. This suggests that pioglitazone alleviates neuropathic pain through attenuation of proinflammatory cytokine upregulation by PPARgamma stimulation.