Antinociception action mechanism

Histamine also induces antinociceptive (i.e. pain-relieving) responses in animals after microinjection into several brain regions [73, 74]. H, and H2 mechanisms are significant and both neuronal and humoral mechanisms may be involved. Brain H2 receptors appear to mediate some forms of endogenous analgesic responses, especially those elicited by exposure to stressors [75]. Many of the modulatory actions of histamine discussed above appear to be activated as part of stress responses. For reasons that remain unclear, histamine releasers, such as thioperamide, show only mild, biphasic antinociceptive actions, even though histamine is a potent and effective analgesic substance. Outside the brain, both H and H3 receptors exist on certain types of sensory nerves and activation of these receptors promotes and inhibits, respectively, peripheral nerve transmission related to pain and/or inflammation [76,77]. 

Idanpaan, J. J., Kalso, E. A., Seppala, T.. Antinociceptive actions of dexmedetomidine and the K-opioid agonist U-50488H against noxious thermal, mechanical and inflammatory stimuli, J. Pharmacol. Exp. Ther. 1994, 271, 1306-1313. 

Second, the mechanisms by which altered K+ channels contribute to the development of chronic pain states and what needs must be met by the channels in order to constitute attractive drug targets with respect to the problem of ensuring a specific antinociceptive action will be discussed. Corresponding examples for this will be given. 

Cheng JK, Chiou LC (2006) Mechanisms of the antinociceptive action of gabapentin. J Pharmacol Sci 100 471-86... 

A number of in vivo pharmacological studies reported that amino acid substitution in position 6 of 14-O-methyloxymorphone (48) afforded derivatives 55-60 that produce potent antinociceptive actions via peripheral mechanisms after s.c. administration in different pain models such as acute nociception i.e. tail-flick test [68], inflammatory pain i.e. formalin test [68] and carrageenan-induced hindpaw inflammation [75] and visceral pain i.e. acetic acid-induced writhing test [93]. In the tail-flick test in the rat, the 6-amino acid derivatives were 19- to 209-fold more potent than morphine (Table 7) and showed similar potency to fentanyl after s.c... 

Rheedia gardneriana, a plant used in traditional medicine in Brazil, contains some biflavonoids that exhibit antinocicetive effects. 13-narin-II8-4 -Ome-eridictyol is a biflavonoid which contains a methoxyl group in position 4 of ring-II. It has revealed potent dose-dependent antinociceptive action during writhing and formalin tests. Results have shown that the effect of this biflavonoid against the second phase of the formalin test was not associated with inhibition of paw oedema. Further studies are necessary to elucidate the mechanism of this compound [94]. 

The involvement of a cholinergic component in the mechanism of action of morphine was proposed even before acetylcholine (ACh) had been shown positively to be present in the central nervous system. Slaughter and Munsell [70] demonstrated that the antinociceptive action of morphine in the cat was potentiated by concurrent administration of neostigmine, an inhibitor of the enzyme cholinesterase, a Rnding later confirmed in man [71,72]. Since then, a number of investigations have attempted to implicate ACh in morphine analgesia [73]. 

Goncales CEP, Araldi D, Panatieri R B, Rocha J B T, Zeni G and Nogueira C W (2005), Antinociceptive properties of acetylenic thiophene and furan derivatives Evidence for the mechanism of action , Life Sciences, 76, 2221-2234. 

Welch, S. P. and Dunlow, L. D. Antinociceptive activity of intrathecally administered potassium channel openers and opioid agonists a common mechanism of action , The Journal of Pharmacology and Experimental Therapeutics 1993, 267, 390-399. 

Figure 2 Schematic model of the intracellular signaling mechanisms including phosphatidylinositol-specific phospholipase C (PI-PLC) isoforms, inositol-1,4,5-triphosphate (IP3) receptor, and protein kinase C (PKC) in the expression of delta opioid receptor agonist-induced spinal antinociception. In addition, PKC is considered to play a substantial role in an intracellular negative feedback action on the spinal delta opioid receptor-mediated antinociceptive pathway.

Lichtman and Martin have shown that cannabinoid-induced antinociception has both spinal and supraspinal components [152]. A spinal a2-noradre-nergic mechanism is involved in cannabinoid antinociception as yohimbine and/or methysergide altered z)9-THC induced antinociceptive effects in rats [153]. A supraspinal mechanism is also involved as cannabinoid analgesia can be produced in spinally transected rats [152], Both similarities and differences were noted on comparison of the antinociceptive effects produced by anandamide (and the more potent fluroanandamide) and d9-THC [154], Anandamide was cross-tolerant to d9-THC, but in contrast to THC, it did not alter opioid-induced antinociceptive effects nor was its action blocked by a k antagonist. 

---