• Jaroslava Buritova, Jean-Pierre Tarayre, Jean-Marie Besson, and Francis Colpaert.
• Centre de Recherche Pierre Fabre, 17 avenue Jean Moulin, 81106 Castres Cedex 06, France. jaroslava.buritova@pierre-fabre.com
• Brain Res. 2003 Jun 6;974(1-2):212-21.

AbstractThe very-high-efficacy, selective 5-HT(1A) receptor agonist, F 13640 produces uniquely powerful analgesia in rat models of chronic pain by novel neuroadaptive mechanisms (inverse tolerance and co-operation with nociception) [Neuropharmacology 43 (2002) 945-958]. A signal transduction theory and evidence suggest that F 13640 initiates these mechanisms, paradoxically, by mimicking the central effects of nociceptive stimulation. We report that the i.p. injection of F 13640 induces c-Fos protein expression in the L3-L5 segments of the spinal cord. Some 65% of c-Fos protein immunoreactive (c-Fos-IR) nuclei occurred bilaterally in the dorsal horn laminae I-II and V-VI, spinal areas that contain neurons responsive to nociceptive stimulation. This pattern is not unlike that found earlier in arthritic rats, a model of somatotopically widespread nociception. Dose-response studies indicated that c-Fos protein expression was induced at doses (0.63 and 2.5 mg/kg, i.p.) at which previous studies had found F 13640 to produce hyperalgesia. Time-response studies found that c-Fos-IR nuclei appeared within 1-4 h after 0.63 mg/kg of F 13640, with a maximum at 2 h. This parallels literature evidence that c-Fos expression reaches peak late after, and outlasts, nociceptive stimulation. Similar to opioids counteracting noxiously induced c-Fos expression, 10 mg/kg (s.c.) of morphine reduced the number of c-Fos-IR nuclei induced by 0.63 mg/kg of F 13640 (by 45+/-5%; P<0.001). The induction by F 13640 of c-Fos protein expression may relate to the initial hyperalgesia which earlier data indicate the agent to produce early upon its administration.

43 keywords...

hide…