Pain
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Operant conditioning mechanisms have been demonstrated to be important in the development of chronic pain. Most experimental studies have investigated the operant modulation of verbal pain reports with extrinsic reinforcement, such as verbal reinforcement. Whether this reflects actual changes in the subjective experience of the nociceptive stimulus remained unclear. ⋯ Results demonstrated that sensitization to prolonged heat-pain stimulation was enhanced by operant learning within 1h. The extent of sensitization was directly dependent on the received magnitude of reinforcement. Thus, operant learning mechanisms based on intrinsic reinforcement may provide an explanation for the gradual development of sustained hypersensitivity during pain that is becoming chronic.
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Peripheral nerve injury produces a persistent neuropathic pain state characterized by spontaneous pain, allodynia and hyperalgesia. In this study, we evaluated the possible involvement of A 2ARs in the development of neuropathic pain and the expression of microglia and astrocytes in the spinal cord after sciatic nerve injury. For this purpose, partial ligation of the sciatic nerve was performed in A 2A knockout mice and wild-type littermates. ⋯ However, a significant decrease of the mechanical allodynia and a suppression of thermal hyperalgesia and allodynia were observed in A 2AR deficient mice. The expression of microglia and astrocytes was enhanced in wild-type mice exposed to sciatic nerve injury and this response was attenuated in knockout animals. Taken together, our results demonstrate the involvement of A 2ARs in the control of neuropathic pain and propose this receptor as an interesting target for the development of new drugs for the management of this clinical syndrome.
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Various mechanisms at peripheral, spinal and/or supraspinal levels may underlie neuropathic pain. The nervous system's capacity for long-term reorganisation and chronic pain may result from abnormalities in RVM facilitatory On cells. Hence, via brainstem injections of the toxic conjugate dermorphin-saporin, which specifically lesions facilitatory cells expressing the mu-opioid receptor (MOR), we sought to determine the influence of these cells in normal and spinal nerve-ligated (SNL) rats. ⋯ During the early stages of nerve injury, or following medullary MOR cell ablation, PGB is ineffective at inhibiting spinal neuronal responses possibly due to quiescent spinal 5HT(3) receptors. This can however be overcome, and PGB's efficacy restored, by pharmacologically mimicking the descending drive at the spinal level with a 5HT(3) receptor agonist. Since RVM facilitatory neurones are integral to a spino-bulbo-spinal loop that reaches brain areas co-ordinating the sensory and affective components of pain, we propose that activity therein may influence painful outcome following nerve injury, and responsiveness to treatment.