Antinociception produced by an ascending spino-supraspinal pathway

Abstract

Studies in mice and rats have shown that antinociception produced by intrathecal (i.t.) administration of opioids can be partially inhibited by intracerebroventricular (i.c.v.) administration of naloxone. In this study we tested the hypothesis that this inhibition by i.c.v. naloxone results from antagonism of supraspinal endogenous opioid-mediated antinociception produced by the action of i.t. opioids on an ascending antinociceptive pathway. In rats lightly anesthetized with urethane/alpha-chloralose, i.t. DAMGO, i.t. lidocaine, or spinal transection at T5-T6 all attenuated the trigeminal jaw opening reflex (JOR) (i.e., were antinociceptive), an effect that was antagonized in each case by i.c.v. naloxone. These findings support the suggestion that there exists a pathway that ascends from the spinal cord to a supraspinal site that tonically inhibits antinociception mediated by supraspinal opioids. When activity in this ascending pathway is suppressed (e.g., by i.t. opioids or local anesthetics or by spinal cord transection), antinociception mediated by supraspinal opioids is disinhibited. To determine the supraspinal site(s) at which endogenous opioid-dependent antinociception is evoked by i.t. opioids, we microinjected naloxone methiodide into several supraspinal sites. Microinjection of naloxone methiodide into nucleus accumbens but not into the rostral ventral medulla (RVM) or the periaqueductal gray matter (PAG) antagonized the suppression of the JOR produced by i.t. DAMGO or lidocaine. The possibility that this ascending pathway may represent a source of spinal input to mesolimbic circuitry involved in setting the state of sensorimotor reactivity to noxious stimuli is discussed.

Decreased Central μ-Opioid Receptor Availability in Fibromyalgia

“…This heterogeneous pattern of reduced binding may reflect different underlying mechanisms operating in these diverse pain conditions. In the case of FM the reductions in MOR BP observed were localized in regions known to be involved in antinociception in animal models (Gear and Levine, 1995;Manning, 1998), as well as pain and emotion regulation, including the affective quality of pain, in humans (Rainville et al, 1997;Zubieta et al, 2001Zubieta et al, , 2003 (i.e., dorsal anterior cingulate, nucleus accumbens, and amygdala). Prolonged activations of the MOR by sustained elevations of endogenous agonist have been shown to result in a subsequent decrease in the concentration of MORs in animal models of chronic pain (Li et al, 2005).…”

Neonatal ethanol exposure produces a hyperalgesia that extends into adolescence, and is associated with increased analgesic and rewarding properties of nicotine in rats

“…Clearly, many analgesic drugs produce dependence, and there is good evidence for direct connections between neural pathways subserving reward and analgesia (Gear et al 1995(Gear et al , 1999Hirakawa et al 2000). Drugs are not intrinsically rewarding due to analgesic properties alone, but may become rewarding in individuals experiencing physical discomfort (Franklin et al 1998).…”

Mechanisms in Chronic Multisympton Illnesses

“…Opioid activity in the nucleus accumbens and the amygdala has been shown to modulate nociceptive neural transmission in animal models of pain (Gear and Levine, 1995;Manning, 1998). Indeed, endogenous opioids play a central role in analgesia and the perception of painful stimuli (Fields, 2004).…”