The European journal of neuroscience
-
Iatrogenic trigeminal nerve injuries remain a common and complex clinical problem. Satellite glial cell (SGC) activation, associated phosphorylation of extracellular signal-regulated kinase (ERK), and neuropeptide expression in the trigeminal ganglion (TG) are known to be involved in trigeminal neuropathic pain related to trigeminal nerve injury. However, the involvement of these molecules in orofacial neuropathic pain mechanisms is still unknown. ⋯ Reduced thresholds to mechanical and heat stimulation to the tongue in LNC rats were also significantly recovered following CGRP8-37 or PD98059 administration. The present findings suggest that CGRP released from TG neurons activates SGCs through ERK1/2 phosphorylation and TG neuronal activity is enhanced, resulting in the tongue hypersensitivity associated with lingual nerve injury. The phenotypic switching of large myelinated TG neurons expressing CGRP may account for the pathogenesis of tongue neuropathic pain.
-
The role of the neuropeptide calcitonin gene-related peptide (CGRP) is well established in nociceptive behaviors. CGRP is highly expressed in the projection pathway from the parabrachial nucleus to the laterocapsular region of the central amygdala (CeC), which plays a critical role in relaying nociceptive information. The CeC is a key structure in pain behavior because it integrates and modulates nociceptive information along with other sensory signals. ⋯ Furthermore, the bilateral tactile allodynia 6 h post-inflammation was significantly decreased in the CGRP KO mice. In contrast, the acute nociceptive behavior immediately after the formalin injection was reduced only at 20-25 min post-injection in the CGRP KO mice. These results suggest that endogenous CGRP contributes to peripheral inflammation-induced synaptic plasticity in the amygdala, and this plasticity may underlie the exaggerated nociception-emotion linkage in pain chronification.