Neuronal Endothelin a Receptor Mediates Experimental and Clinical Vascular Pain through an Endothelial-Neural Axis.

Vascular dysfunction causes vascular pain (VP), the most common clinical manifestation of prevalent vascular diseases, while the mechanisms remain elusive. Mouse models are developed by mimicking peripheral vascular diseases and combining multiple strategies to demonstrate that primary sensory neuronal endothelin A receptor (ETAR) mediates experimental and clinical VP through an endothelial-neural axis. Endothelial cells (ECs), but not macrophages or smooth muscle cells (SMCs), release endothelin-1 (ET-1) and directly activate primary sensory neurons by binding to ETAR on sensory neurons, resulting in VP.

Optogenetic Activation of Peripheral Somatosensory Neurons in Transgenic Mice as a Neuropathic Pain Model for Assessing the Therapeutic Efficacy of Analgesics.

Optogenetics is a novel biotechnology widely used to precisely manipulate a specific peripheral sensory neuron or neural circuit. However, the use of optogenetics to assess the therapeutic efficacy of analgesics is elusive. In this study, we generated a transgenic mouse stain in which all primary somatosensory neurons can be optogenetically activated to mimic neuronal hyperactivation in the neuropathic pain state for the assessment of analgesic effects of drugs.

Transcriptional profiles of TGF-β superfamily members in the lumbar DRGs and the effects of activins A and C on inflammatory pain in rats.

Signaling by the transforming growth factor (TGF)-β superfamily is necessary for proper neural development and is involved in pain processing under both physiological and pathological conditions. Sensory neurons that reside in the dorsal root ganglia (DRGs) initially begin to perceive noxious signaling from their innervating peripheral target tissues and further convey pain signaling to the central nervous system. However, the transcriptional profile of the TGF-β superfamily members in DRGs during chronic inflammatory pain remains elusive.

Transcriptional Profiling of TGF-β Superfamily Members in Lumbar DRGs of Rats Following Sciatic Nerve Axotomy and Activin C Inhibits Neuropathic Pain.

Background: Neuroinflammation and cytokines play critical roles in neuropathic pain and axon degeneration/regeneration. Cytokines of transforming growth factor-β superfamily have implications in pain and injured nerve repair processing. However, the transcriptional profiles of the transforming growth factor-β superfamily members in dorsal root ganglia under neuropathic pain and axon degeneration/regeneration conditions remain elusive.

Deletion of MyD88 adaptor in nociceptor alleviates low-dose formalin-induced acute pain and persistent pain in mice.

The myeloid differentiation factor 88 (MyD88) adaptor mediates signaling by Toll-like receptors and some interleukins (ILs) in neural and non-neuronal cells. Recently, MyD88 protein was found to express in primary sensory neurons and be involved in the maintenance of persistent pain induced by complete Freund's adjuvant, chronic constriction injury and chemotherapy treatment in rodents. However, whether MyD88 in nociceptive neurons contributes to persistent pain induced by intraplantar injection of formalin remains elusive.

Cytokine activin C ameliorates chronic neuropathic pain in peripheral nerve injury rodents by modulating the TRPV1 channel.

Background And Purpose: The cytokine activin C is mainly expressed in small-diameter dorsal root ganglion (DRG) neurons and suppresses inflammatory pain. However, the effects of activin C in neuropathic pain remain elusive.

Experimental Approach: Male rats and wild-type and TRPV1 knockout mice with peripheral nerve injury - sciatic nerve axotomy and spinal nerve ligation in rats; chronic constriction injury (CCI) in mice - provided models of chronic neuropathic pain.