Pain
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According to the Generalized Hypervigilance Hypothesis (GHH) of McDermid et al., the unpleasantness of sensory stimuli, rather than their modality, determines whether they will be perceptually amplified in hypervigilant persons. In a test of this idea, ratings of the intensity of sensations evoked by cutaneous and auditory stimuli were obtained from individuals with chronic myofascial pain (fibromyalgia, temporomandibular disorders), and from (less hypervigilant) healthy control participants. ⋯ In both cases, perceptual amplification extended to even the lowest stimulus intensities, a result that is not consistent with the predictions of the GHH. An alternative formulation, the attentional gain control model of hypervigilance, is proposed, according to which those types of stimuli that are associated with pain are amplified because of the attention that is habitually directed toward them.
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Area-specific representation of mechanical nociceptive stimuli within SI cortex of squirrel monkeys.
While functional imaging studies in humans have consistently reported activation of primary somatosensory cortex (SI) with painful stimuli, the specific roles of subdivisions of areas 3a, 3b, and 1 within SI during pain perception are largely unknown, particularly in the representation of mechanical evoked pain. In this study, we investigated how modality, location, and intensity of nociceptive stimuli are represented within SI by using high-spatial resolution optical imaging of intrinsic signals in Pentothal-anesthetized squirrel monkeys. Perceptually comparable mechanical nociceptive and innocuous tactile stimuli were delivered by indenting the glabrous skin of the distal finger pads with 0.2 and 2mm diameter probes, respectively. ⋯ However, with innocuous tactile stimulation, mainly areas 3b and 1 exhibited response modulation with different levels of stimulation. In summary, mechanical nociceptive inputs are area-specific and topographically represented within SI. We propose that all areas of SI are implicated in encoding the features of mechanical nociception, where areas 3a and 3b are distinctively involved in coding nociceptive and pressure sensation components of stimulation.
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Ionotropic gamma-aminobutyric acid (GABA(A)) receptors control the relay of nociceptive signals at several levels of the neuraxis. Experiments with systemically applied benzodiazepines, which enhance the action of GABA at these receptors, have suggested both anti- and pronociceptive effects. The interpretation of such experiments has been notoriously difficult because of confounding sedation. ⋯ The relative contributions of these subunits were alpha2 approximately alpha3>alpha5, and thus very similar to those found for intrathecal diazepam (0.09 mg/kg). Accordingly, SL-651498 (10mg/kg, p.o.), an "anxioselective" benzodiazepine site agonist with preferential activity at alpha2/alpha3 subunits, significantly reduced formalin-induced flinching in wild-type mice. We conclude that systemic diazepam exerts a genuine antihyperalgesic effect, which depends on spinal GABA(A) receptors containing alpha2 and/or alpha3 subunits.
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Osteoarthritis (OA) is a debilitating and painful disease, the incidence of which increases with advancing age. One of the confounding aspects of OA is that there is a disconnect between the severity of joint degeneration and the intensity of pain reported. This study examined the relationship between age, joint nociception, and joint pathology in an animal model of naturally occurring OA. ⋯ Micro-CT and histopathological determination of OA positively correlated with age; however, there was no significant correlation between the severity of joint degeneration and nociception. In the Dunkin Hartley model of inveterate OA, the level of joint pathology correlates well with increasing age. This study also provides the first objective evidence that there is no correlation between joint nociception and articular damage, thereby corroborating the clinical observation that pain is a poor predictor of OA severity.