Increased substance P and synaptic remodeling occur in the trigeminal sensory system with sustained osteoarthritic temporomandibular joint sensitivity.

Abstract

Temporomandibular joint (TMJ) pain is among the most prevalent musculoskeletal conditions and can result from atypical joint loading. Although TMJ pain is typically self-resolving, 15% of patients develop chronic TMJ pain that is recalcitrant to therapy and may be attributed to changes in pain processing centers. Although TMJ overloading induces pain and osteoarthritis, whether neuronal modifications in the trigeminal sensory system contribute to persistent TMJ pain is unknown. This study investigates changes in excitatory neuropeptides and synaptic transmission proteins in cases of transient and persistent TMJ sensitivity in a rat model. Rats underwent repeated jaw loading that produces transient (2N-load) or persistent (3.5N-load) sensitivity. In both groups, immunolabeling was used to assess substance P in the spinal trigeminal nucleus caudalis (Sp5C) and glutamate transporter 1 in the ventroposteriomedial thalamus early after loading. Synaptosomal Western blots were used to measure synaptic proteins in the caudal medulla and thalamus at a later time after loading. Substance P increases transiently in the Sp5C early after loading that induces persistent sensitivity. However, glutamate transporter 1 is unchanged in the ventroposteriomedial thalamus. At a later time, synaptosomal Western blots show loss of the presynaptic tethering protein, synapsin, and the inhibitory scaffolding protein, gephyrin, in the thalamus with persistent, but not transient, sensitivity. No changes are identified in synapsin, phosphorylated synapsin, homer, or gephyrin in the caudal medulla. Substance P in the Sp5C and later loss of inhibitory synapses in the thalamus likely contribute to, or indicate, persistent TMJ pain.