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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Pain can be considered as a signal of "bodily error": errors put organisms at danger and activate behavioral defensive systems. If the error is of physical nature, pain is the warning signal that motivates protective action such as avoidance behavior to safeguard our body's integrity. Interestingly, an important component of neural error processing, the error-related negativity (ERN), has been found to be related to avoidance in anxiety disorders. ⋯ In contrast to earlier findings in anxiety disorders, individuals with elevated ERN amplitudes did not engage in more pain-related avoidance behavior. In fact, the opposite pattern was found at the start of acquisition: individuals with higher compared with lower ERN amplitudes were slower in learning to avoid pain. Replications and future studies on the relationship between ERN and avoidance behavior are needed.
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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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Afferents from the C2 spinal nerve (SN) and trigeminal nerve (TN) innervate neighboring cranial territories, and their convergence on the upper cervical dorsal horn neurons represents neural substrate of pain referral in primary headache disorders. Unfortunately, little is known about trigeminocervical input to the major spinal nociceptive projection area lamina I. Here, we used ex vivo brainstem-cervical cord preparation for the visually guided whole-cell recording from the upper cervical lamina I neurons. ⋯ Thus, trigeminocervical input in lamina I is processed in both nerve-specific and convergent circuitries. Afferent convergence on to inhibitory interneurons serves as a feedforward mechanism balancing excitatory drive to projection neurons. Disruption of this balance may cause pain in primary headache syndromes.