SPINAL SEROTONERGIC RECEPTORS MEDIATE FACILITATION OF A NOCICEPTIVE REFLEX BY SUBCUTANEOUS FORMALIN INJECTION INTO THE HINDPAW IN RATS

It is documented that spinal nociceptive transmission receives descend ing facilitatory and inhibitory-modulation from supraspinal structures . The rostral ventral medulla (RVM), including the nucleus raphe magnu s (NRM), nuclei reticularis gigantocellularis (NGC) and gigantocellula ris pars alpha (NGC alpha), is the major bulbar relay of descending mo dulatory influences. Pharmacological studies show that facilitation of a spinal nociceptive tail-flick (TF) reflex induced by stimulation in the NGC and NGC alpha is mediated by spinal serotonergic receptors. T he present series of experiments provide evidence that activation of s pinal serotonergic systems are critical for both induction and mainten ance of secondary hyperalgesia induced by subcutaneous injection of fo rmalin into one hindpaw. Subcutaneous injection of formalin produced f acilitation of tail withdrawal (mechanical) and the TF reflex (thermal ). Facilitatory effects persisted for at least 30 min. Peripheral bloc kade of the activity by local injection of a hydrophilic lidocaine der ivative (QX-314, 5%) into the injected hindpaw abolished both mechanic al and thermal facilitation, indicating that peripheral input is impor tant to maintain long-lasting facilitation. Intrathecal application of a serotonergic receptor antagonist methysergide at a dose (61 nmol) w hich completely blocked descending facilitation produced by electrical - or chemical-stimulation in the NGC and NGC alpha also significantly attenuated or completely abolished facilitation of tail withdrawal and the TF reflex induced by formalin. Methysergide was effective whether the injection was performed before or after the formalin injection. T hese results suggest that activation of descending facilitatory seroto nergic influences by a prolonged noxious stimulation could contribute to secondary hyperalgesia observed at the tail. (C) 1998 Elsevier Scie nce B.V. All rights reserved.