Rapid communication
Analgesia by direct antagonism of nociceptor sensitization involves the arginine-nitric oxide-cGMP pathway

https://doi.org/10.1016/0014-2999(92)90881-4Get rights and content

Abstract

We tested the hypothesis that activation of the nitric oxide (NO)-cGMP pathway is involved in the mechanism of two directly acting non-opiate peripheral analgesics, myrcene and dipyrone, using our modification of the Randall-Selitto test. The NO inhibitor, NG-monomethyl-L-arginine (50 μg/paw) and methylene blue (500 μg/paw) abolished the analgesic effect of dipyrone and myrcene. Dibutyryl cyclic adenosine monophosphate (DbcAMP) caused a dose-dependent hyperalgesia (20, 50 and 100 μg/paw). Only responses to low doses of DbcAMP were inhibited by the two analgesics. Pretreatment with MY5445 (50 μg/paw) resulted in potentiation of the effects of both analgesics. These results support our hypothesis that the sensitivity of nociceptors may be controlled by the balance between the levels of cAMP and cGMP. Stimulation of the NO-cGMP pathway is probably the common denominator for the mode of action of peripheral analgesics which block hyperalgesia directly.

References (7)

There are more references available in the full text version of this article.

Cited by (197)

  • Peripheral nitric oxide signaling directly blocks inflammatory pain

    2020, Biochemical Pharmacology
    Citation Excerpt :

    The involvement of the NO pathway in the peripheral analgesic actions of other drugs and endogenous substances has also been extensively investigated. There is evidence that peripheral cannabinoids (a CB1-dependent effect), PPAR-γ agonists, xylazine, hormones such as estradiol and melatonin, bovine lactoferrin, choline (via alpha-7 nicotinic receptors), hydrogen sulfide releasing drugs, phosphodiesterase inhibitors, and pertussis toxin engage the NO-cGMP signaling to promote peripheral antinociception in various experimental models of inflammatory pain [81,83,137,138,149–158]. In addition, not only did these analgesic drugs and endogenous substances elicit peripheral analgesia through the activation of the NO pathway, but there was also compelling evidence that alternative therapies such as electroacupuncture and natural products (e.g., plant extracts, venoms, and toxins) also required the integrity of this pathway to exert peripheral analgesia [152,159–165].

View all citing articles on Scopus
View full text