Pain
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Spinal projection neurons are a major pathway through which somatic stimuli are conveyed to the brain. However, the manner in which this information is coded is poorly understood. ⋯ In addition, optogenetic experiments reveal that cold-selective SPB neurons do not receive input from Nos1 inhibitory interneurons and, compared with other SPB neurons, show significantly smaller inhibitory postsynaptic currents upon activation of Pdyn inhibitory interneurons. Together, these data suggest that cold output from the spinal cord to the parabrachial nucleus is mediated by a specific cell type with distinct properties.
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Dissecting the organization of circuit pathways involved in pain affect is pivotal for understanding behavior associated with noxious sensory inputs. The central nucleus of the amygdala (CeA) comprises distinct populations of inhibitory GABAergic neurons expressing a wide range of molecular markers. CeA circuits are associated with aversive learning and nociceptive responses. ⋯ We find that monosynaptic PBn input is preferentially organized to molecularly specific neurons in distinct subdivisions of the CeA. The spared nerve injury model of neuropathic pain differentially altered PBn monosynaptic excitatory input to CeA neurons based on molecular identity and topographical location within the CeA. These results provide insight into the functional organization of affective pain pathways and how they are altered by chronic pain.
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The bladder is innervated by primary afferent nerve fibres that detect bladder distension and, through projections into the spinal cord, provide sensory input to the central nervous system circuits regulating bladder sensation and function. Uropathogenic E. coli (UPEC) bacteria are the primary cause of urinary tract infection (UTI) in adults, inducing clinical symptoms characterised by exaggerated bladder sensation, including urgency, frequency, and pelvic pain. However, the mechanisms underlying UTI-induced modulation of bladder afferent function are yet to be explored. ⋯ Further evaluation revealed that UPEC supernatants exclusively sensitised high-threshold bladder mechanoreceptors to graded bladder distension and also recruited a population of "silent nociceptors" to become mechanosensitive, thereby amplifying bladder afferent responses to physiological stimuli. UPEC supernatants contained significantly elevated concentrations of a range of cytokines released from innate immune cells, including but not limited to TNF-α, IL-1β, IL-6, IL-17, IFN-gamma, and MCP-1. These data provide novel mechanistic insight into how UPEC-mediated UTI induces bladder hypersensitivity and the symptoms of frequency, urgency, and pelvic pain.