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Although the opioids are the principal treatment options for moderate to severe pain, their use is also associated with the development of tolerance, defined as the progressive need for higher doses to achieve a constant analgesic effect. The mechanisms which underlie this phenomenon remain unclear. Recent studies revealed that cholecystokinin (CCK) is(More)
Shocked rats (Rattus norvegicus) often exhibit longer tail withdrawal latencies to radiant heat, which suggests that exposure to shock reduces pain. But at the same time, rats appear hyperreactive to shock, suggesting than pain is enhanced. Experiment 1 replicated these findings and showed that when tail movement was monitored, shocked rats were less(More)
Relief of pain is rewarding. Using a model of experimental postsurgical pain we show that blockade of afferent input from the injury with local anesthetic elicits conditioned place preference, activates ventral tegmental dopaminergic cells, and increases dopamine release in the nucleus accumbens. Importantly, place preference is associated with increased(More)
Nerve injury can produce hypersensitivity to noxious and normally innocuous stimulation. Injury-induced central (i.e. spinal) sensitization is thought to arise from enhanced afferent input to the spinal cord and to be critical for expression of behavioral hypersensitivity. Descending facilitatory influences from the rostral ventromedial medulla have been(More)
BACKGROUND & AIMS Pain is a main complaint of patients with pancreatitis. We hypothesized that such pain is mediated through ascending pathways via the nucleus gracilis (NG) and is dependent on descending facilitatory influences from the rostral ventromedial medulla (RVM). METHODS A rat model of persistent experimental pancreatitis was used. After(More)
Dorsal root injury results in substantial and often irreversible loss of sensory functions as a result of the limited regenerative capacity of sensory axons and the inhibitory barriers that prevent both axonal entry into and regeneration in the spinal cord. Here, we describe previously unknown effects of the growth factor artemin after crush injury of the(More)
It is held that the tail-flick test of pain depends on a spinal reflex because a similar response is observed in spinally transected rats. But when subjects were manually held and a cool heat setting was used, supraspinal systems facilitated the response (Experiment 1). This effect did not depend on the rate at which the tail was heated (Experiment 2) but(More)
A puzzling observation is why peripheral nerve injury results in chronic pain in some, but not all, patients. We explored potential mechanisms that may prevent the expression of chronic pain. Sprague Dawley (SD) or Holtzman (HZ) rats showed no differences in baseline sensory thresholds or responses to inflammatory stimuli. However, spinal nerve ligation(More)
Opioids can induce hyperalgesia in humans and in animals. Mechanisms of opiate-induced hyperalgesia and possibly of spinal antinociceptive tolerance may be linked to pronociceptive adaptations occurring at multiple levels of the nervous system including activation of descending facilitatory influences from the brainstem, spinal neuroplasticity, and changes(More)
Rats exposed to a few moderately intense (1 mA) shocks subsequently exhibit lower vocalization thresholds to shock and thermal stimuli. They also exhibit facilitated learning in a Pavlovian conditioning paradigm. Together, these results suggest that shock exposure can enhance pain (hyperalgesia). The present study examined the role of the amygdala and bed(More)