Pain
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The current study examined patients with temporomandibular disorders (TMD) (n=20) and pain-free controls (n=28) under stress and relaxation conditions. Interleukin-6 (IL-6), norepinephrine and epinephrine (NE and E) were measured both before and during each of two conditions: a non-stressful relaxation period and a speech stressor. Ischemic pain sensitivity was also assessed after each of these conditions. ⋯ After controlling for depressed mood, TMD patients as a whole showed a significantly blunted response in IL-6 levels produced during stress as compared to controls (beta=0.31*). Although TMD subjects as a whole did not show the expected greater pain sensitivity to the ischemic task, those displaying a less optimistic style did exhibit lower pain tolerance times (beta=-0.61*) and higher pain unpleasantness ratings (beta=0.48*), compared with low optimism controls and high optimism TMD patients. Less optimistic TMD patients also had higher NE and IL-6 levels during stress than other TMD patients, while optimism was unrelated to responses in controls (*P<0.05).
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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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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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Recent studies demonstrate the possible existence of tonic modulatory control of nociceptive input mediated by spinal cannabinoid receptors (CB1). Accordingly, it is predicted that a reduction in the spinal CB1 receptors may enhance sensitivity to sensory stimuli and a decrease in spinal antinociceptive potency to cannabinoid agonists. An antisense oligodeoxynucleotide (ODN) specific to the CB1 receptor was used to 'knock-down' CB1 receptors in the lumbar spinal cord and dorsal root ganglia by the local, repeated intrathecal (i.th.) administration of the ODN. ⋯ These data support the possibility of endogenous inhibitory cannabinoid tone to limit spinal afferent input of thermal and tactile stimuli. Lifting of this inhibitory tone through a 'knock-down' of spinal CB1 receptors apparently lowers the thresholds for sensory input, as reflected by the actions of MK-801 to block tactile and thermal hypersensitivity. The increased spinal dynorphin may act to further promote afferent outflow and abnormal pain because sequestration of spinal dynorphin with antiserum also reverses the manifestations of abnormal pain following knock-down of CB1 receptors.
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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.