Articles: hyperalgesia.
-
Anesthesia and analgesia · Sep 2004
Randomized Controlled Trial Clinical TrialThe effect of intravenous infusion of adenosine on electrically evoked hyperalgesia in a healthy volunteer model of central sensitization.
Human pain models invoking central sensitization, one of the key mechanisms of chronic pain, may be useful for characterizing new analgesics. A new model of electrical hyperalgesia can detect the efficacy of several analgesic mechanisms. Because IV adenosine can alleviate neuropathic pain, we investigated its effect on experimental sensitization. ⋯ Thus, in accordance with reports on neuropathic pain, adenosine reduced central sensitization in the human model of electrical hyperalgesia. However, adenosine did not have the long-term effects seen in patients. The model can investigate mechanisms of drugs for the treatment of chronic pain.
-
One consequence of repeated drug administration is the development of adaptations in the nervous system, sometimes termed 'drug-opposite' responses. During administration, the effects of the drug are diminished by these adaptations (tolerance), while cessation of drug use results in the emergence of these drug-opposite responses as the withdrawal syndrome. Recent evidence on pain responses challenges this simple notion of withdrawal and suggests that aversive drug-opposite states may play a more important role in drug dependence than previously thought. ⋯ Thus, for pain and mood, the chronic opioid user under the influence of the drug does not experience an opioid effect diminished by tolerance but a state opposite to the effect of the drug. Increases in drug concentration arising from administration serve only to reduce the degree of pain and mood disturbance. These aversive pain and mood states may contribute to the motivation for continued drug use and the dysfunction associated with drug dependence.
-
N-methyl-D-aspartate (NMDA) receptors serve prominent roles in vast physio-pathological conditions including hyperalgesia (defined as augmented pain intensity in response to painful stimuli) associated with central sensitization. Using M40403 a synthetic low molecular weight superoxide dismutase mimetic that removes superoxide we show for the first time that this radical plays a key role in NMDA-mediated hyperalgesia. Intrathecal administration of NMDA in rats led to a time-dependent development of thermal hyperalgesia. ⋯ M40403 by preventing MnSOD nitration restored its activity and inhibited the hyperalgesic response to intrathecal NMDA. Thus, superoxide-mediated nitration and deactivation of spinal MnSOD is a novel pathway of NMDA-mediated spinal hyperalgesia and hence central sensitization since it helps to maintain high levels of superoxide that in turn maintains nociceptive signaling. The broader implication of our findings is that superoxide may contribute to various forms of pain events that are driven by NMDA-receptor activation.
-
Amputation of a segment of the tail produced long-lasting changes in nociception and morphine-induced antinociception. Plastic changes in nociceptive transmission may occur at the spinal cord as well as supraspinal structures after tail amputation. ⋯ Morphine induced facilitation of the hot-plate (HP) response at a low dose and a greater dose of morphine is required to produce complete inhibition of the HP response. Since these effects happen at five weeks after the surgery, tail amputation may serve as a mouse model for studying long-term plastic changes in central nervous system after amputation.
-
The present experiments examined the role of spinal proinflammatory cytokines [interleukin-1beta (IL-1)] and chemokines (fractalkine) in acute analgesia and in the development of analgesic tolerance, thermal hyperalgesia, and tactile allodynia in response to chronic intrathecal morphine. Chronic (5 d), but not acute (1 d), intrathecal morphine was associated with a rapid increase in proinflammatory cytokine protein and/or mRNA in dorsal spinal cord and lumbosacral CSF. To determine whether IL-1 release modulates the effects of morphine, intrathecal morphine was coadministered with intrathecal IL-1 receptor antagonist (IL-1ra). ⋯ Fractalkine may be exerting these effects via IL-1 because fractalkine (CX3CL1) induced the release of IL-1 from acutely isolated dorsal spinal cord in vitro. Finally, gene therapy with an adenoviral vector encoding for the release of the anti-inflammatory cytokine IL-10 also potentiated acute morphine analgesia and attenuated the development of tolerance, hyperalgesia, and allodynia. Taken together, these results suggest that IL-1 and fractalkine are endogenous regulators of morphine analgesia and are involved in the increases in pain sensitivity that occur after chronic opiates.