Pain
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Pain due to tissue injury is often characterized by the presence of hyperalgesia and allodynia. It is hypothesized that these perceptual states are mediated by sensitization of peripheral terminals of primary afferent neurons together with several changes in the central nervous system. This provides a rationale for preemptive analgesia, whereby the blockade of primary afferent input prior to injury may result in a reduction of post-injury pain. ⋯ We observed that PLGA/bupivacaine reduces inflammatory hyperalgesia, edema and hyperthermia in a temporal and dose-related fashion in awake animals. Moreover, we demonstrated that PLGA/bupivacaine has a prolonged inhibitory effect on the tissue levels of substance P and bradykinin in the inflamed hindpaws. The results of these studies clearly indicate the potential therapeutic utility of the PLGA bupivacaine system, with the single dose administration producing a prolonged suppression of hyperalgesia, edema and biochemical indices of inflammation.
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The aim of this study was to investigate the analgesic effects of epidural opioids upon persistent pain sensitivity in neonatal rat pups. Two models of persistent pain were used, subcutaneous injection of carrageenan, and topical application of capsaicin cream, both to the hind paw. The contribution of individual opioid receptor subtypes in the spinal cord to analgesia were tested at different developmental stages using epidural mu (morphine sulphate), delta (DPDPE) and kappa (U69593) opioid receptor agonists in neonatal rats aged P (postnatal day) 3, 10 and 21. ⋯ The results show that newborn rat pups are capable of displaying both allodynia and hyperalgesia following experimental inflammation that is blocked by epidural mu, delta and kappa opioids. The opioid potency is enhanced compared with antinociception in acute tests. This is not observed following capsaicin hyperalgesia and is therefore not a general consequence of C fibre induced increases in central excitability but relies upon mechanisms special to inflammatory pain.
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The possible role of spinal prostanoids in the tactile allodynia and thermal hyperalgesia associated with an experimental model of neuropathic pain was investigated. Neuropathic pain was induced by tight ligation of the L5 and L6 spinal nerves. Tactile allodynia was assessed 7 days after the surgery by measuring hindpaw withdrawal threshold to probing with von Frey filaments. ⋯ Finally, morphine, but not ketorolac, given i.th. produced dose-dependent anti nociception in either the tail-flick or the paw-flick tests. However, there was no synergy between morphine and ketorolac against thermal nociception in either of the tests. These findings suggest that spinal prostanoids produced via both COX1 and COX2 pathways may play a role in neuropathic pain states and suggest the clinical utility of opioid plus COX-inhibitor combination therapy.
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Injection of a dilute solution of formalin into a rat hindpaw produces a biphasic nociceptive response consisting of an early phase during the first 5 min after formalin injection and a later phase starting after 15 min and lasting for 40-50 min. The period between the two phases of nociceptive responding is generally considered to be a phase of inactivity. We compared the nociceptive behaviors produced by a single hindpaw injection of 50 microl of formalin with those produced by two formalin injections given 20 min apart. ⋯ As these data were obtained from pentobarbital-anesthetized, spinalized rats, the data suggest further that the two excitatory phases and the active inhibition are mediated by spinal mechanisms and that the inhibition is not under regulation of a GABAergic mechanism. The implication of the results is not only further evidence of physiological control mechanisms interacting to regulate pain, but they also indicate the overriding priority of intrinsic inhibitory mechanisms. This, in turn, suggests that the clinical management of pain may be enhanced by efforts to potentiate mechanisms of inhibition.
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Withdrawal reflex responses to graded von Frey filaments applied to the plantar surface of the paw were measured before and after bone hole damage in rats with either a dorsal column (DC) lesion or a sham DC lesion. Two methods were employed to produce models of osteotomy; a small hole was drilled through either the (1) tibia or (2) calcaneus (Houghton, A. K., Hewitt, E. and Westlund, K. ⋯ Nocifensive behavior, characterized by a lifting and guarding of the damaged limb, was also observed in animals with a hole through the calcaneus. In contrast, we found that interrupting the dorsal column pathway with a small mid-line lesion (1 week prior to the osteotomy) prevented the development of both the primary and secondary mechanical hyperalgesia and allodynia but not the guarding of the damaged limb. This study provides evidence that axons in the medial part of the dorsal column are involved in the development of mechanical hyperalgesia and allodynia after bone hole injury.