Brain circuits for pain and its treatment.

Pain is a multidimensional experience with sensory-discriminative, affective-motivational, and cognitive-evaluative components. Pain aversiveness is one principal cause of suffering for patients with chronic pain, motivating research and drug development efforts to investigate and modulate neural activity in the brain's circuits encoding pain unpleasantness. Here, we review progress in understanding the organization of emotion, motivation, cognition, and descending modulation circuits for pain perception. We describe the molecularly defined neuron types that collectively shape pain multidimensionality and its aversive quality. We also review how pharmacological, stimulation, neurofeedback, surgical, and cognitive-behavioral interventions alter activity in these circuits to relieve chronic pain.

Orofacial Movements Involve Parallel Corticobulbar Projections from Motor Cortex to Trigeminal Premotor Nuclei.

How do neurons in orofacial motor cortex (MCtx) orchestrate behaviors? We show that focal activation of MCtx corticobulbar neurons evokes behaviorally relevant concurrent movements of the forelimb, jaw, nose, and vibrissae. The projections from different locations in MCtx form gradients of boutons across premotor nuclei spinal trigeminal pars oralis (SpVO) and interpolaris rostralis (SpVIr). Furthermore, retrograde viral tracing from muscles that control orofacial actions shows that these premotor nuclei segregate their outputs. In the most dramatic case, both SpVO and SpVIr are premotor to forelimb and vibrissa muscles, while only SpVO is premotor to jaw muscles. Functional confirmation of the superimposed control by MCtx was obtained through selective optogenetic activation of corticobulbar neurons on the basis of their preferential projections to SpVO versus SpVIr. We conclude that neighboring projection neurons in orofacial MCtx form parallel pathways to distinct pools of trigeminal premotor neurons that coordinate motor actions into a behavior.

Vibrissa Self-Motion and Touch Are Reliably Encoded along the Same Somatosensory Pathway from Brainstem through Thalamus.

Active sensing involves the fusion of internally generated motor events with external sensation. For rodents, active somatosensation includes scanning the immediate environment with the mystacial vibrissae. In doing so, the vibrissae may touch an object at any angle in the whisk cycle. The representation of touch and vibrissa self-motion may in principle be encoded along separate pathways, or share a single pathway, from the periphery to cortex. Past studies established that the spike rates in neurons along the lemniscal pathway from receptors to cortex, which includes the principal trigeminal and ventral-posterior-medial thalamic nuclei, are substantially modulated by touch. In contrast, spike rates along the paralemniscal pathway, which includes the rostral spinal trigeminal interpolaris, posteromedial thalamic, and ventral zona incerta nuclei, are only weakly modulated by touch. Here we find that neurons along the lemniscal pathway robustly encode rhythmic whisking on a cycle-by-cycle basis, while encoding along the paralemniscal pathway is relatively poor. Thus, the representations of both touch and self-motion share one pathway. In fact, some individual neurons carry both signals, so that upstream neurons with a supralinear gain function could, in principle, demodulate these signals to recover the known decoding of touch as a function of vibrissa position in the whisk cycle.