Pain
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This paper reports an experimental investigation of engagement with and disengagement from a threatening cue of pain. As most paradigms in pain research only provide an overall index of attentional deployment by pain-related information, a new paradigm was developed that allowed an independent investigation of engagement with and disengagement from pain cues. Forty pain-free volunteers performed a cueing task in which they had to detect pain targets and tone targets as quickly and as accurately as possible. ⋯ However, when pain was cued and did not occur, there was retardation in disengagement from the pain cue. This retardation was more pronounced and extended across time in those high in catastrophic thinking about pain. On examination it appeared that catastrophic thinking about pain may operate by a protection of the belief that the cue for pain is a valid one, despite experience to the contrary.
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Neuropathic pain syndromes are characterized by spontaneous pain and by stimulus-evoked allodynia and hyperalgesia. Stimulus-induced pain, i.e. the capacity of external stimuli to alter sensory processing so as to generate a pain hypersensitivity that outlasts the initiating stimulus, is usually present only after intense activation of nociceptors. In abnormal pain states, however, such as after capsaicin injection or inflammation, a stimulus-induced incremental pain can be generated by repetitive light touch, termed progressive tactile hypersensitivity (PTH). ⋯ However, 10 weeks and after, the same repeated stimulation induced a progressive tactile hypersensitivity that persisted after discontinuation of the tactile stimulation. Following SNI, repeated stimulation of the hypersensitive skin territory, corresponding to the intact spared sural nerve, never induced PTH. Tactile stimulation of regenerating afferents but not spared non-injured afferents, can induce, therefore, PTH and such a stimulus-induced alteration in pain processing may contribute to clinical neuropathic pain.
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There is extensive evidence that spinal excitatory amino acids (EAAs) like glutamate (Glu) and aspartate (Asp) are important in the processing of nociceptive behaviors caused by incisions. To better understand EAA-induced dorsal horn sensitization caused by surgery, we examined the time course and extent of spinal amino acid (AA) release during and after a plantar incision utilizing in vivo microdialysis. We also examined the role of primary afferent input and axonal conduction by measuring spinal EAAs in rats after hindpaw denervation and in rats treated with spinal tetrodotoxin (TTX). ⋯ The concentrations of AAs returned to baseline by 1h. The percentage increase is in some cases less and for a shorter period of time compared to other models of persistent pain, perhaps because the incision injury is less severe compared to others models. This profile of EAA release further explains why models of inflammation and chemical irritation do not translate well to human postoperative pain.
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Transcutaneous electrical nerve stimulation (TENS) partially reduces primary hyperalgesia and is frequency dependent such that high frequency TENS produces approximately a 30% reduction in hyperalgesia whereas low frequency TENS has no effect. Both high and low frequency TENS completely reduce secondary hyperalgesia by activation of mu and delta- opioid receptors in the spinal cord and rostral-ventral medulla suggesting an opiate mediated analgesia. Clonidine in combination with opiates produces a synergistic interaction such that there is a potentiated reduction in hyperalgesia. ⋯ The ED50s for heat and mechanical hyperalgesia following low frequency TENS with clonidine were 0.002 and 0.2 mg/kg, respectively and those following high frequency TENS with clonidine were 0.005 and 0.15 mg/kg, respectively. Thus, combined use of clonidine and TENS enhances the reduction in analgesia produced by TENS and enhances the potency of clonidine. It would thus be expected that one would reduce the side effects of clonidine and enhance analgesic efficacy with combinations of pharmaceutical and non-pharmaceutical treatments.
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Although known primarily for its role in neuronal development, brain-derived neurotrophic factor (BDNF) has also recently been implicated in processes mediated by the adult nervous system, such as spinal nociception. Peripheral inflammation increases expression of BDNF preferentially in dorsal root ganglion cells that contain substance P and/or calcitonin gene-related peptide, known nociceptive transmitters for which synthesis is also increased during inflammatory states. Expression of the tyrosine kinase receptor that selectively binds BDNF, trkB, is increased in the spinal dorsal horn during inflammation as well. ⋯ FL-mediated mechanism, the i.t. administration of another trkB ligand, neurotrophin-4/5, also produces hyperalgesia while the trkC agonist neurotrophin-3, which weakly cross-reacts with trkB, has little effect. Finally, with the accumulating evidence linking BDNF to synaptic plasticity, we investigated whether BDNF-induced hyperalgesia in normal mice involves the N-methyl-D-aspartate (NMDA) receptor. Interestingly, i.t. co-administration of the NMDA receptor antagonist D(-)-2-amino-5-phosphonovaleric acid (D-APV) with BDNF dose-dependently inhibits BDNF-induced hyperalgesia, suggesting that BDNF induces acute hyperalgesic responses and affects central sensitization in a process dependent on NMDA receptor activation.