EVIDENCE FOR A PERIPHERAL ORIGIN OF THE TONIC NOCICEPTIVE RESPONSE TOSUBCUTANEOUS FORMALIN

The orofacial formalin test in the rat is a valid and reliable model o f nociception and is sensitive to various classes of analgesic drugs. The noxious stimulus consists in an injection of diluted formalin (2.5 % in saline) into the upper lip. The behavioural nociceptive response is measured in terms of the amount of time the animal spends rubbing t he injected area. Two distinct periods of intense rubbing activity can be identified, a first phase occurring in the first 3 min and a secon d phase lasting from 12 to 39 min after formalin injection. The presen t study verified the peripheral origin of the first phase of the forma lin response and examined whether the second phase is produced by peri pheral activation of afferent fibres and/or by a phenomenon of central facilitation induced by the neural activity that occurs during the fi rst phase. This was determined by assessing the effect of a local anae sthetic agent (lidocaine) administered into the formalin injection sit e, before or after the first phase of the formalin response. Local inj ection of 50 mu l of lidocaine prior to formalin completely abolished the first phase of the formalin response but this blockade did not sig nificantly influence the appearance and development of the second phas e. Thus, the primary afferent activity that normally occurs during the first phase of the formalin response is not a prerequisite for the ex pression of the second phase. A higher dose of lidocaine (150 mu l) in duced, in addition, inhibition of the first part of the second phase. Fifty or 150 mu l of lidocaine injected after the first phase produced a blockade of the second phase, with a dose-dependent duration (6 min and 18 min, respectively). Our results` demonstrated that both the fi rst and second phases of the nociceptive response to formalin depend o n primary afferents activation and, consequently, that the second phas e cannot be mediated by central sensitisation alone.