A Lateralized Deficit in Morphine Antinociception after Unilateral Inactivation of the Central Amygdala

Abstract

The amygdala is a forebrain region that is receiving increasing attention as a modulator of pain sensation. The amygdala contributes to antinociception elicited by both psychological factors (e.g., fear) and exogenous opioid agonists. Unlike the midbrain periaqueductal gray matter (PAG) or rostral ventromedial medulla, the amygdala is a pain-modulating region that has clear bilateral representation in the brain, making it possible to determine whether pain-modulating effects of this region are lateralized with respect to the peripheral origin of noxious stimulation. Unilateral inactivation of the central nucleus of the amygdala (Ce) plus adjacent portions of the basolateral amygdaloid complex (with either the excitotoxin NMDA or the GABA A agonist muscimol) reduced the ability of morphine to suppress prolonged, formalin-induced pain derived from the hindpaw ipsilateral, but not contralateral, to the inactivated region. This effect was evident regardless of the nociceptive scoring method used (weighted scores or flinch-frequency method) and was not accompanied by a concurrent reduction in morphine-induced hyperlocomotion. Unilateral lesions restricted to the basolateral amygdaloid complex (i.e., not including the Ce) did not reduce the ability of morphine to suppress formalin-induced pain derived from either hindpaw. The results constitute the first report of a lateralized deficit in opioid antinociception after unilateral inactivation of a specific brain area and show the first clear neuroanatomical dissociation between antinociceptive and motor effects of systemically administered morphine in the rat. The amygdala appears to modulate nociceptive signals entering the ipsilateral spinal dorsal horn, probably through monosynaptic connections with ipsilateral portions of the PAG.

The affective component of pain in rodents: Direct evidence for a contribution of the anterior cingulate cortex

“…During the formalin experiments, acute formalin-induced nociceptive behaviors were quantified on the conditioning days. A trained rater scored formalin-induced nociceptive behaviors simultaneously using both the rating scale and flinch frequency methods (25). Scoring was carried out over the entire duration of the conditioning session (50 min) by using time bins of 5 min each.…”

Bilateral behavioral and regional cerebral blood flow changes during painful peripheral mononeuropathy in the rat

“…Bernard and colleagues (1989Bernard and colleagues ( ,1990Bernard and colleagues ( ,1996 have demonstrated a spino(trigemino)pontoamygdaloid pathway that may be involved with the affective-motivational dimension of pain. Conversely, anatomical and electrophysiological studies indicate the existence of an efferent pathway originating in the amygdala, synapsing within the periaquaductal gray and continuing on to the spinal cord dorsal horn that modulates pain (Hopkins and Holstege 1978;Krettek and Price 1978;Beitz 1982;Watson et al, 1983;Zhang et al, 1991;Bernard et al, 1996;Manning 1998). In addition, the basal ganglia receives nociceptive information through several sources including the amygdala, cingulate cortex, prefrontal cortex and the habenula (Ma and Han, 1991;Cenci et al, 1992;Ma et al, 1992;Chudler and Dong, 1995).…”

Modulation of Conditioned Fear, Fear-Conditioned Analgesia, and Brain Regional C-Fos Expression Following Administration of Muscimol into the Rat Basolateral Amygdala

“…footshock) display conditioned analgesia results in both the expression of fear-related behaviour (e.g. freezing and 22-kiloHertz ultrasonic vocalisations) 10, 49 and robust analgesia -as a consequence of activating the descending inhibitory pain pathway 27,32,37,43 .…”