Morphine induces peripherally μ-opioid-mediated antinociception to heat but not to mechanical stimulation. Peripheral sigma-1 receptors tonically inhibit μ-opioid antinociception to mechanical stimuli, but it is unknown whether they modulate μ-opioid heat antinociception. We hypothesized that sigma-1 receptors might play a role in the modality-specific peripheral antinociceptive effects of morp...

BACKGROUND Several studies have shown that muscarinic cholinergic agonists cause antinociception in humans and animals when given by both spinal and non-spinal parenteral routes. It is uncertain which subtype of muscarinic receptor is involved in spinally mediated antinociceptive effects caused by these drugs. The cholinergic receptor agonists McN-A-343 (M1 selective; 3.89 to 389 nmol) and carb...

Current evidence for sex-based nociception and antinociception, largely confined to behavioral measures of pain sensitivity, chronic pain syndromes, and analgesic efficacy, provides little mechanistic insights into biological substrates causally associated with sexual dimorphic pain experience. Spinal cord has been shown to be a central nervous system region in which regulation of opioid antino...

IAntinociceptive at the spinal level Adding NA is antinociceptive The story gets complicated because NA both inhibits and facilitates spinal nociceptive reflexes Spinal NA increases with acute and chronic nociceptive stimuli. NA tonically induces antinociception NA spinal denervation produces hyper and hypoalgesia NA spinal denervation retards the appearance of autotomy and neuropathic pain NA ...

Capsaicin depolarizes primary afferent C-fibers releasing substance P (SP) whose N-terminal metabolites appear to play a role in the development of antinociception. Because some effects of SP(1-7) are similar to those of zinc, we tested the hypothesis that zinc in the extracellular area plays a role in capsaicin-induced antinociception, as measured using the abdominal stretch (writhing) assay. ...

The role of dynorphin A (1-17; Dyn) and its associated kappa opioid receptor (KOR) in nociception represents a longstanding scientific conundrum: Dyn and KOR (Dyn/KOR) have variously been reported to inhibit, facilitate, or have no effect on pain. We investigated whether interactions between sex and pain type (which are usually ignored) influenced Dyn/KOR-mediated antinociception. Blockade of t...

In this study, the influence of dopamine receptor agonists and antagonists on antinociception induced by bac10fen has been examined in the formalin test. The GABA-B agonist bac10fen induced antinociception in both phases of the formalin test in mice. The dopamine receptor agonists SKF 38393 and quinpirole also induced antinociception in both phases of the test. SKF 38393 but not quinpirole ...

Nociceptin/orphanin FQ (N/OFQ) is the endogenous peptide for the NOP receptors. Depending on the doses, intrathecal administration of N/OFQ has dual actions (ie, hyperalgesia and antinociception) in rodents. However, the pharmacological profile of intrathecal N/OFQ is not fully known in primates. The aim of this study was to investigate behavioral effects of intrathecal N/OFQ over a wide dose r...

This study was undertaken to test the hypothesis that P-glycoprotein (P-gp) modulates opioid peptide pharmacodynamics. [D-Penicillamine2, 5]enkephalin (DPDPE) (10 mg/kg i.v.) was administered to mdr1a(-/-) and wild-type mice to assess systemic disposition and antinociception. A subsequent dose-response experiment examined the impact of P-gp on DPDPE antinociception. In addition, the time course...