ENHANCED NOCICEPTIVE BEHAVIOR FOLLOWING CONDITIONING INJECTION OF FORMALIN IN THE PERIORAL AREA OF THE RAT

The possible existence of long-term modifications in response to a tra nsient nociceptive conditioning stimulation was investigated in the ra t in three experiments. (1) A nociceptive conditioning stimulus was de livered in the form of a s.c. formalin injection (conditioning injecti on) in the left upper lip. Evaluation of the nociceptive behaviour tri ggered by another formalin injection (testing injection) made in the c ontrolateral right upper lip was carried out in distinct groups of rat s 7, 14 or 28 days after the conditioning. An enhanced nociceptive res ponse at days 7 and 14 and a return to the baseline at day 28 were obs erved. (2) A similar protocol was developed with formalin used for bot h conditioning and testing but an anaesthetic blockade of the infraorb ital nerve was performed just before the conditioning injection to sup press the initial barrage. The change observed at day 7 was suppressed by the nerve block. (3) A conditioning nociceptive stimulus was appli ed either ipsilaterally to the right lower lip or to the tail. An incr eased nociceptive response was observed when the conditioning stimulus was applied to the same side as the test stimulus but no increase in the formalin test response was detected when the conditioning stimulus was applied to the tail. These results indicated that, after a single formalin injection in the left upper lip, a hyperexcitability develop ed that depended on the initial barrage, lasted for at least 2 weeks, was no longer present at 4 weeks and might rely on a segmental mechani sm. The hypothesis of a central sensitization triggered by an initial barrage and maintained by an ongoing input induced from the periphery is discussed.