Pain
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Daily life consists of a chain of decisions. Typically, individuals may choose to pursue what they already know (exploitation) or to search for other options (exploration). This exploration-exploitation dilemma is a topic of interest across multiple scientific fields. ⋯ Second, participants weighted rewards more heavily than receiving pain. Finally, after receiving a painful outcome, participants were more inclined to explore than to exploit a rewarding movement. We argue that by focusing more on how individuals in pain solve the exploration-exploitation dilemma is helpful in understanding behavioral decision making in pain.
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Gain-of-function and loss-of-function mutations in Nav1.7 cause chronic pain and pain insensitivity, respectively. The preferential expression of Nav1.7 in the peripheral nervous system and its role in human pain signaling make Nav1.7 a promising target for next-generation pain therapeutics. However, pharmacological agents have not fully recapitulated these pain phenotypes, and because of the lack of subtype-selective molecular modulators, the role of Nav1.7 in the perception of pain remains poorly understood. ⋯ Makatoxin-3 acts on the S3-S4 loop of voltage sensor domain IV (VSD4) of Nav1.7, which causes a hyperpolarizing shift in the steady-state fast inactivation and impairs inactivation kinetics. We also determined the key residues and structure-function relationships for the toxin-channel interactions, which are distinct from those of other well-studied α toxins. This study not only reveals a new mechanism underlying BV-evoked pain but also enriches our knowledge of key structural elements of scorpion toxins that are pivotal for toxin-Nav1.7 interactions, which facilitates the design of novel Nav1.7 selective modulators.
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Although it is clear that osteoarthritis (OA) pain involves activation and/or sensitization of nociceptors that innervate knee joint articular tissues, much less is known about the role of the innervation of surrounding bone. In this study, we used monoiodoacetate (MIA)-induced OA in male rats to test the idea that pain in OA is driven by differential contributions from nerves that innervate knee joint articular tissues vs the surrounding bone. The time-course of pain behavior was assayed using the advanced dynamic weight-bearing device, and histopathology was examined using haematoxylin and eosin histology. ⋯ Changes in the function of bone afferent neurons were only observed at day 28, when there was histological evidence of damage to the articular cartilage and subchondral bone. Our findings suggest that pain early in MIA-induced OA involves activation and sensitization of nerves that innervate the joint capsule but not the underlying subchondral bone, and that pain in late MIA-induced OA involves the additional recruitment of nerves that innervate the subchondral bone. Thus, nerves that innervate bone should be considered important targets for development of mechanism-based therapies to treat pain in late OA.
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Randomized Controlled Trial
Evaluation of the effect of analgesic treatment on signs of nociception-related behaviors during physiotherapy in patients with disorders of consciousness: a pilot crossover randomized controlled trial.
Neuro-orthopedic disorders are common in patients with disorders of consciousness (DOC) and can lead to potential pain. However, the patients' inability to communicate makes pain detection and management very challenging for clinicians. In this crossover randomized double-blind placebo-controlled study, we investigated the effects of an analgesic treatment on the presence of nociception-related behaviors. ⋯ This study highlights that physiotherapy may be potentially painful for patients with DOC, while analgesic treatments did not reduced NCS-R scores. Therefore, careful monitoring with appropriate assessment and treatment before and during mobilization should become a priority in clinical settings. Future studies should focus on the development of assessment tools sensitive to analgesic dosage to manage pain in DOC.
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Randomized Controlled Trial
Cognitive therapy, mindfulness-based stress reduction, and behavior therapy for the treatment of chronic pain: a single-blind randomized controlled trial.
Trials of cognitive therapy (CT), mindfulness-based stress reduction (MBSR), and behavior therapy (BT) suggest that all 3 treatments produce reductions in pain and improvements in physical function, mood, and sleep disturbance in people with chronic pain conditions. Fewer studies have compared the relative efficacies of these treatments. In this randomized controlled study, we compared CT, MBSR, BT, and treatment as usual (TAU) in a sample of people with chronic low back pain (N = 521). ⋯ Weekly assessments allowed us to assess rates of change; ie, how quickly a given treatment produced significant differences, compared with TAU, on a given outcome. The 3 treatments differed significantly from TAU on average by session 6, and this rate of treatment effect was consistent across all treatments. Results suggest the possibility that the specific techniques included in CT, MBSR, and BT may be less important for producing benefits than people participating in any techniques rooted in these evidence-based psychosocial treatments for chronic pain.