oxadiazoles and Nociceptive-Pain

Despite the availability of the current drug arsenal for pain management, there is still a clinical need to identify new, more effective, and safer analgesics. Based on our earlier study, newly synthesized 1,3,4-oxadiazole derivatives of pyrrolo[3,4-

Topics: Analgesics; Animals; Dinoprostone; Gastric Mucosa; Male; Nociception; Nociceptive Pain; Oxadiazoles; Pain Measurement; Peroxidase; Pyridazines; Pyrroles; Rats; Rats, Wistar

Endogenous carbon monoxide (CO), which is produced by the enzyme heme oxygenase (HO), participates as a neuromodulator in physiological processes such as thermoregulation and nociception by stimulating the formation of 3',5'-cyclic guanosine monophosphate (cGMP). In particular, the acute physical restraint-induced fever of rats can be blocked by inhibiting the enzyme HO. A previous study reported that the HO-CO-cGMP pathway plays a key phasic antinociceptive role in modulating noninflammatory acute pain. Thus, this study evaluated the involvement of the HO-CO-cGMP pathway in antinociception induced by acute stress in male Wistar rats (250-300 g; n=8/group) using the analgesia index (AI) in the tail flick test. The results showed that antinociception induced by acute stress was not dependent on the HO-CO-cGMP pathway, as neither treatment with the HO inhibitor ZnDBPG nor heme-lysinate altered the AI. However, antinociception was dependent on cGMP activity because pretreatment with the guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) blocked the increase in the AI induced by acute stress.

Topics: Acute Pain; Animals; Carbon Monoxide; Cyclic GMP; Deuteroporphyrins; Heme; Heme Oxygenase (Decyclizing); Lysine; Male; Nociceptive Pain; Oxadiazoles; Pain Measurement; Rats, Wistar; Signal Transduction; Stress Disorders, Traumatic, Acute