Pain
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Interstitial cystitis/bladder pain syndrome (IC/BPS) is a prevalent, chronic bladder disorder that negatively impacts the quality of life for ∼5% of the western population. Hypersensitivity of mechanosensory afferents embedded within the bladder wall is considered a key component in mediating IC/BPS symptoms. Bladder infusion of voltage-gated sodium (Nav) channel blockers show clinical efficacy in treating IC/BPS symptoms; however, the current repertoire of Nav channels expressed by and contributing to bladder afferent function is unknown. ⋯ In vivo intrabladder infusion of TTX significantly reduces activation of dorsal horn neurons within the spinal cord to bladder distension. These data provide the first comprehensive analysis of Nav channel expression within sensory afferents innervating the bladder. They also demonstrate an essential role for TTX-S Nav channel regulation of bladder-innervating DRG neuroexcitability, bladder afferent responses to distension, and nociceptive signalling to the spinal cord.
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The left dorsolateral prefrontal cortex (DLPFC) is involved in the experience and modulation of pain, and may be an important node linking pain and cognition. Repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC can reduce chronic and experimental pain. However, whether left DLPFC rTMS can influence the development of chronic pain is unknown. ⋯ There was a trend toward improved cognitive function with rTMS compared with sham (P = 0.057). These data indicate that repeated left DLPFC rTMS reduces the pain severity in a model of prolonged muscle pain. The findings may have implications for the development of sustained pain in clinical populations.
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Changes in brain function in chronic pain have been studied using paradigms that deliver acute pain-eliciting stimuli or assess the brain at rest. Although motor disability accompanies many chronic pain conditions, few studies have directly assessed brain activity during motor function in individuals with chronic pain. Using chronic jaw pain as a model, we assessed brain activity during a precisely controlled grip force task and during a precisely controlled pain-eliciting stimulus on the forearm. ⋯ Second, although stimulus intensity and pain perception were similar between the groups, functional activity in brain regions including the dorsal lateral prefrontal cortex, rostral ventral premotor cortex, and inferior parietal lobule best separated the groups. Our observations suggest that chronic jaw pain is associated with changes in how the brain processes motor and pain-related information even when the effector producing the force or experiencing the pain-eliciting stimulus is distant from the jaw. We also demonstrate that motor tasks and multivariate analyses offer alternative approaches for studying brain function in chronic jaw pain.
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Changes in activity patterns frequently accompany the experience of chronic pain. Two activity patterns, avoidance and overdoing, are hypothesized to contribute to the development of ongoing pain and pain-related disability, while activity pacing is frequently introduced to enhance pain management and functioning. Two studies were conducted to assess whether reliable subgroups with differing activity patterns could be identified in different pain populations and to evaluate changes in these subgroups after a group format, pain management program. ⋯ Individuals who used high levels of activity pacing and low levels of avoidance consistently reported significantly better functioning relative to all other individuals. Observed changes in activity patterns from pre-treatment to post-treatment suggested that decreasing the association between activity pacing and avoidance was associated with better functioning. These results have implications for both the assessment of activity pacing and for its use as an intervention in the management of ongoing pain.
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Modulation of pain may result from engagement of opioid receptors in multiple brain regions. Whether sensory and affective qualities of pain are differentially affected by brain opioid receptor circuits remains unclear. We previously reported that opioid actions within the rostral anterior cingulate cortex (ACC) produce selective modulation of affective qualities of neuropathic pain in rodents, but whether such effects may occur in other areas of the ACC is not known. ⋯ Activation of mu opioid receptors within specific rostral ACC circuits, however, selectively modulates affective dimensions of ongoing pain without altering withdrawal behaviors. These data suggest that RVM and ACC opioid circuits differentially modulate sensory and affective qualities of pain, allowing for optimal behaviors that promote escape and survival. Targeting specific ACC opioid circuits may allow for treatment of chronic pain while preserving the physiological function of acute pain.