No abstract

Neuropathic pain is often caused by injury and diseases that affect the somatosensory system. Although pain development has been well studied, pain recovery mechanisms remain largely unknown. Here, we found that CD11c-expressing spinal microglia appear after the development of behavioral pain hypersensitivity following nerve injury. Nerve-injured mice with spinal CD11c + microglial depletion failed to recover spontaneously from this hypersensitivity. CD11c + microglia expressed insulin-like growth factor-1 (IGF1), and interference with IGF1 signaling recapitulated the impairment in pain recovery. In pain-recovered mice, the depletion of CD11c + microglia or the interruption of IGF1 signaling resulted in a relapse in pain hypersensitivity. Our findings reveal a mechanism for the remission and recurrence of neuropathic pain, providing potential targets for therapeutic strategies.

Chronic pain is a major public health problem that currently lacks effective treatment options. Here, a method that can modulate chronic pain-like behaviour induced by nerve injury in mice is described. By combining a transient nerve block to inhibit noxious afferent input from injured peripheral nerves, with concurrent activation of astrocytes in the somatosensory cortex (S1) by either low intensity transcranial direct current stimulation (tDCS) or via the chemogenetic DREADD system, we could reverse allodynia-like behaviour previously established by partial sciatic nerve ligation (PSL). Such activation of astrocytes initiated spine plasticity to reduce those synapses formed shortly after PSL. This reversal from allodynia-like behaviour persisted well beyond the active treatment period. Thus, our study demonstrates a robust and potentially translational approach for modulating pain, that capitalizes on the interplay between noxious afferents, sensitized central neuronal circuits, and astrocyte-activation induced synaptic plasticity.

The indications for immune checkpoint inhibitors (ICIs) have expanded to include carcinomas of various organs. However, as ICI therapy expands, the management of immune-related adverse events (irAEs) has become a problem. ICI-related pancreatitis and cholangitis are relatively rare irAEs. Although some patients with ICI-related pancreatitis and cholangitis are asymptomatic and do not require treatment, there have been reports of patients who did not respond to immunosuppressive therapy and died. Thus, the pathogenesis of ICI-related pancreatitis and cholangitis should be clarified immediately. Currently, the role of endoscopy in the diagnosis and treatment of inflammatory pancreatic and biliary duct diseases is becoming increasingly important. In this review, we summarize clinical characteristics as well as radiographic and endoscopic findings of ICI-related pancreatitis and cholangitis.

The role of astrocytes in the spinal dorsal horn (SDH) for sensory information processing under normal conditions is poorly understood. In this study, we investigated whether SDH astrocytes respond to noxious and innocuous stimuli to the skin of normal mice using in vivo two-photon Ca imaging under anesthesia. We found that noxious stimulation evoked by intraplantar formalin injection provoked an elevation in intracellular Ca levels in SDH astrocytes. By contrast, neither instantaneous noxious pinching nor innocuous stimuli (cooling or brushing) to the hindpaw elicited astrocytic Ca responses. Thus, SDH astrocytes could respond preferentially to a strong and/or sustained noxious stimulus.