ABSTRACT
Cannabinoids suppress behavioral and neurophysiological responses to noxious stimuli in rodents when administered systemically. The purpose of this study was to extend previous studies of the site of cannabinoid analgesia. Rats were tested in the tail flick test before and after microinjections of the cannabinoid agonist WIN55, 212-2 (5 microg) into one of 17 different brain regions. WIN55,212-2 significantly elevated tail-flick latencies when injected into the amygdala, the lateral posterior and submedius regions of the thalamus, the superior colliculus and the noradrenergic A5 region. By contrast, pain behavior was unaffected by microinjections of the cannabinoid into the other 11 areas examined (prefrontal cortex, nucleus accumbens, lateral hypothalamus, substantia nigra, cuneiform nucleus, anterior pretectal, intralaminar, parafasicular, posterior, thalamic nuclei, as well as the ventral medial, ventral lateral nuclei in the posterior thalamus).
Subject(s)
Cannabinoids/pharmacology , Nociceptors/drug effects , Pain/drug therapy , Amygdala/drug effects , Amygdala/physiology , Analgesics/pharmacology , Animals , Benzoxazines , Brain Chemistry/drug effects , Male , Microinjections , Morpholines/pharmacology , Naphthalenes/pharmacology , Norepinephrine/physiology , Pain Measurement/drug effects , Rats , Rats, Sprague-Dawley , Reaction Time/drug effects , Superior Colliculi/drug effects , Superior Colliculi/physiology , Thalamus/drug effects , Thalamus/physiologyABSTRACT
Surgical lesions of the cingulum bundle in humans produce marked decreases in severe pain associated with cancer, reflex sympathetic dystrophy and other forms of chronic pain. Similarly, a temporary block of the anterior cingulum bundle in the rat by microinjection of lidocaine produces significant decreases in formalin-pain and reduces autotomy following peripheral neurectomy. The present study explored the effect of electrical stimulation of the cingulum bundle/surrounding cortical tissue (CB/CT) on tonic pain in the rat. Experiment 1 examined changes in formalin-induced pain responses following a 2.5-min period (30 s/min for 5 min) of electrical stimulation of the CB/CT 15 min prior to the formalin injection. The stimulation produced a significant reduction of first-period and second-period pain responses. Experiment 2 examined changes in formalin-induced pain responses following a 2.5-min period (30 s/min for 5 min) of electrical stimulation of the CB/CT 20 min following the formalin injection. The stimulation produced a dramatic reduction in second-period pain responses which persisted for the duration of the 35-min post-stimulation test period. The fact that either electrical stimulation or surgical section of the CB/CT produces pain relief suggests that this region serves a complex role in pain processing. Since the cingulum bundle has major connections with all other structures of the limbic system, it is possible that electrical stimulation disrupts patterned activity in the system, which is known to play an especially important role in the affective-motivational dimension of pain.
