Orofacial pain frequently originates from pathologic conditions in the masticatory muscles or temporomandibular joints (TMJs). The mediators and mechanisms that monitor
pain and
inflammation, centrally or peripherally, are of great interest in the search for new treatment modalities. The
neuropeptides substance P (SP),
calcitonin gene-related peptide (CGRP), and
neuropeptide Y (NPY) have all been found at high levels in the synovial fluid of arthritic TMJs in association with spontaneous
pain, while
serotonin (5-HT) has been found in association with
hyperalgesia/
allodynia of the TMJ.
Interleukin-1 beta (IL-1 beta) and
tumor necrosis factor alpha (
TNF alpha) have been found in arthritic TMJs, but not in healthy TMJs, in association with
hyperalgesia/
allodynia of the TMJ as well as spontaneous
pain. Anterior
open bite, which may be a clinical sign of TMJ destruction, has been found in association with high levels of CGRP, NPY, and
IL-1 beta in the synovial fluid of the TMJ.
Interleukin-1 beta has also been related to radiographic signs of joint destruction.
Prostaglandin E2 (
PGE2) and
leukotriene B4 (
LTB4) are both present in the arthritic TMJ, and
PGE2 has been shown to be associated with
hyperalgesia/
allodynia of the TMJ. Very little is known about
pain and inflammatory mediators in muscles. However, we know that
5-HT and
PGE2 are involved in the development of
pain and
hyperalgesia/
allodynia of the masseter muscle in patients with
fibromyalgia, whereas local
myalgia (myofascial
pain) seems to be modulated by other, as yet unknown mediators. Interaction between the peripheral nervous system (sensory and sympathetic nerves), the immune system, and local cells is probably of great importance for the modulation of
pain and
inflammation in the TMJ and orofacial musculature.