Chronic treatments with aspirin or acetaminophen reduce both the development of polyarthritis and Fos-like immunoreactivity in rat lumbar spinal cord.
We have previously shown that during the development of adjuvant-induced arthritis (AIA), and without any peripheral stimulation, the number of Fos-like immunoreactive (Fos-LI) neurons in lumbar spinal cord increases in parallel with the clinical and behavioral signs of the disease and peaks 3 weeks after the inoculation which corresponds to the maximal stage of hyperalgesia (Abbadie and Besson 1992a). The aim of this study was to evaluate the suitability of the Fos-LI technique to gauge the effects of the two most prescribed analgesics, aspirin and acetaminophen (paracetamol), on spinal cord neurons of polyarthritic rats. The effects of the two drugs were tested on the "evoked" Fos-LI induced by peripheral mechanical noxious stimulus, as well as the effects of a chronic treatment on "basal" Fos-LI appearing during the development of polyarthritis in the absence of any intentional stimulation. We showed that: (1) Fos-LI evoked by ankle stimulation was not modified by either aspirin (150 mg/kg i.v.) or pro-acetaminophen (300 mg/kg i.v.) injection or by a 10-day chronic treatment with acetaminophen (250 or 500 mg/kg/day). (2) Despite the fact that the clinical signs of arthritis were reduced, basal Fos-LI induced by AIA disease was not changed after a 2-week chronic treatment with either aspirin (300 mg/kg/day) or acetaminophen (500 mg/kg/day) starting 3 weeks after AIA inoculation, i.e., at the maximal stage of hyperalgesia and when Fos-LI is maximal. This observation questions the suitability of Fos-LI technique to gauge the effects of mild analgesics. (3) In contrast, when the same chronic treatment was applied during the development of AIA, i.e., 1 week after inoculation, the number of Fos-LI nuclei was significantly decreased (about 50%) in aspirin- and acetaminophen-treated groups as compared to vehicle-treated groups. In parallel, the clinical signs of AIA disease were blocked by the two drug treatments. In addition, 2 weeks after the end of treatment, neither the clinical signs nor the number of Fos-LI increased again. The fact that the two drugs are able to prevent c-fos expression during development of arthritis, but not to interfere with already existing c-fos expression, suggests that for pharmacological investigations this technique should be used with caution. Thus, the potential use of Fos-LI to gauge the effects of non-steroidal antinociceptive drugs and other mild analgesics during chronic disease such as arthritis is discussed.
Abbadie
Catherine
C
Physiopharmacologie du Système Nerveux, INSERM U161 and EPHE, 75014 ParisFrance.
Besson
Jean-Marie
JM
D000082:Acetaminophen / Q000627:therapeutic use*; D000818:Animals; D001169:Arthritis, Experimental / Q000473:pathology / Q000517:prevention & control*; D001241:Aspirin / Q000627:therapeutic use*; D001360:Avidin; D001710:Biotin; D005620:Freund's Adjuvant; D007150:Immunohistochemistry; D008297:Male; D009161:Mycobacterium; D010544:Peroxidases; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
D016760:Proto-Oncogene Proteins c-fos; D001360:Avidin; D000082:Acetaminophen; D001710:Biotin; D005620:Freund's Adjuvant; D010544:Peroxidases; D001241:Aspirin