Peripheral and central mechanisms of orofacial inflammatory pain
Introduction
The face, mouth, and jaws manifest some of the most common pains in the body, and epidemiological investigations have documented the high prevalence rates for several acute or chronic orofacial pain conditions (Lipton et al., 1993, LeResche and Drangsholt, 2008). These pain conditions include many involving inflammation of orofacial tissues and range from acute pulpitis (toothache) and mucositis to chronic arthritic conditions affecting the temporomandibular joint (TMJ. This article will focus on the mechanisms in orofacial tissues and in nociceptive pathways in the brain that underlie the development or maintenance of acute and chronic orofacial inflammatory pain.
Section snippets
Overview of Trigeminal Primary Afferent Mechanisms
The trigeminal (V) nerve, which is the fifth cranial nerve, provides the principal sensory innervation of the face and mouth (for review, see Dubner et al., 1978, Sessle, 2005a, Sessle, 2009). Many trigeminal primary afferent fibers terminate in the orofacial tissues as free nerve endings and function as nociceptors since they are activated by noxious stimuli. These noxious stimuli may include mechanical stimuli such as a pin prick or surgical incision of the facial skin or oral mucosa,
Effects of Inflammation and Inflammatory Irritants on Various Trigeminal Nociceptive Afferents
Inflammation of peripheral tissues may be associated with the release of chemical mediators from tissue cells such as mast cells, macrophages, and immune cells (e.g. 5-hydroxytrytamine [5-HT], histamine, tumor necrosis factor [TNF]alpha) or from the nociceptive afferent endings themselves (e.g. substance P) (for review, see Hucho and Levine, 2006; Meyer et al., 2006, Woolf and Ma, 2007). Many of these mediators can act on the nociceptive endings at the site of injury to increase their
Overview of Trigeminal Nociceptive Pathways and Organizational Features
The trigeminal primary afferents project to the trigeminal brainstem sensory nuclear complex where they synapse on second-order neurons. The trigeminal brainstem complex can be subdivided into the main or principal sensory nucleus and the spinal tract nucleus, which is comprised of three subnuclei: oralis, interpolaris, and caudalis (Fig. 3). The neurons in each nucleus and subnucleus are arranged in a topographic manner; many are low-threshold mechanoreceptive (LTM) neurons, that provide the
Effects of Inflammation and Inflammatory Irritants on Central Trigeminal Nociceptive Mechanisms
The nociceptive neurons in subnuclei caudalis and oralis and higher centers such as ventrobasal thalamus can be activated not only by noxious mechanical or thermal stimulation of orofacial tissues but also by inflammatory irritants applied to orofacial tissues (e.g. Amano et al., 1986, Broton et al., 1988, Chiang et al., 1998, Burstein et al., 2006, Goadsby, 2006, Zhang et al., 2006, Zanotto et al., 2007, Honda et al., 2008; Yamazaki et al., 2008, Tashiro et al., 2009, Tashiro et al., 2010,
Summary
This article has reviewed current understanding of the peripheral and central mechanisms underlying acute and chronic orofacial inflammatory pain conditions. These conditions may be associated not only with the activation of trigeminal nociceptive primary afferents and neurons in the trigeminal nociceptive pathways in the CNS, but may also produce a sustained hyperexcitability (sensitization) of these neural elements that may contribute to the allodynia, hyperalgesia, spontaneous pain, and pain
References (142)
- et al.
Chemokines and pain mechanisms
Brain Res. Rev.
(2009) - et al.
N-methyl-D-aspartate and non-N-methyl-D-aspartate receptor antagonism reduces fos-like immunoreactivity in central trigeminal neurons after corneal stimulation in the rat
Neurosci.
(1996) - et al.
Trigeminal subnucleus caudalis beyond homologies with the spinal dorsal horn
Pain
(2000) - et al.
Pulpar tooth injury induces plastic changes in S100B positive astroglial cells in the trigeminal subnucleus caudalis
Neurosci. Lett.
(2010) - et al.
Human and animal experimental models of acute and chronic muscle pain: intramuscular algesic injection
Pain
(2004) - et al.
A perfusion technique for the determination of pro-inflammatory mediators induced by intradental application of irritants
J. Pharmacol. Toxicol. Methods
(2001) - et al.
Electrophysiological characterization of the rat trigeminal caudalis (Vc) neurons following intramuscular injection of capsaicin
Neurosci. Lett.
(2010) - et al.
Sexual dimorphism in the antinociception mediated by kappa opioid receptors in the rat temporomandibular joint
Neurosci. Lett.
(2004) - et al.
Dental noxious input reaches the subnucleus caudalis of the trigeminal complex in the rat, as shown by c-fos expression upon thermal or mechanical stimulation
Neurosci. Lett.
(1994) - et al.
Effects of morphine microinjections into the trigeminal sensory complex on the formalin test in the rat
Exp. Neurol.
(1996)
The peripheral antinociceptive effect of morphine in a rat model of facial pain
Neurosci.
Nitric oxide-proton stimulation of trigeminal ganglion neurons increases mitogen-activated protein kinase and phosphatase expression in neurons and satellite glial cells
Neurosci.
Sex-related differences in the distribution of opioid receptor-like 1 receptor mRNA and colocalization with estrogen receptor mRNA in neurons of the spinal trigeminal nucleus caudalis in the rat
Neurosci.
Chemokines, neuronal-glial interactions, and central processing of neuropathic pain
Pharmacol. Ther.
The impact of ethnic differences in response to capsaicin-induced trigeminal sensitization
Pain
Astrocytic control of glutamatergic activity: astrocytes as stars of the show
Trends Neurosci.
Stimulation of craniofacial muscle afferents induces prolonged facilitatory effects in trigeminal nociceptive brainstem neurones
Pain
Signaling pathways in sensitization: toward a nociceptor cell biology
Neuron
Immunohistochemical localization of μ-opioid receptors in human dental pulp
J. Endo.
Responsiveness changes of tooth pulp driven-neurons in thalamic ventral posteromedial and mediodorsal nuclei following experimental pulpitis and naloxone administration in rats
J Oral Biosci.
Deficiency in endogenous modulation of prolonged heat pain in patients with irritable bowel syndrome and temporomandibular disorder
Pain
Peripheral NMDA receptor modulation of jaw muscle electromyographic activity induced by capsaicin injection into the temporomandibular joint of rats
Brain Res.
Surgical incision can alter capsaicin-induced central sensitization in rat brainstem nociceptive neurons
Neurosci.
Glutamate and capsaicin effects on trigeminal nociception I: Activation and peripheral sensitization of deep craniofacial trigeminal nociceptive afferents
Brain Res
Glutamate and capsaicin effects on trigeminal nociception. II: Activation and central sensitization in brainstem neurons with deep craniofacial afferent input
Brain Res
Estimated prevalence and distribution of reported orofacial pain in the United States
JADA
Involvement of medullary dorsal horn glial cell activation in mediation of masseter mechanical allodynia induced by experimental tooth movement
Arch. Oral Biol.
Sensitivity of patients with painful temporomandibular disorders to experimentally evoked pain Evidence for altered temporal summation of pain
Pain
Characterization of a model of chronic orofacial hyperalgesia in the rat: Contribution of NaV 1.8
J. Pain
Central sensitization induced in thalamic nociceptive neurons by tooth pulp stimulation is dependent on the functional integrity of trigeminal brainstem subnucleus caudalis but not subnucleus oralis
Brain Res.
Gliotransmission: Exocytotic release from astrocytes
Brain Res. Rev.
Facial injections of pruritogens and algogens excite partly overlapping populations of primary and second-order trigeminal neurons in mice
J Neurophysiol.
Responses of neurons in feline trigeminal subnucleus caudalis (medullary dorsal horn) to cutaneous, intraoral and muscle afferent stimuli
J. Neurophysiol.
Emerging peripheral receptor targets for deep-tissue craniofacial pain therapies
J. Dent, Res.
Ocular nociceptors
Trigeminal brainstem nuclear complex. Immunohistochemistry and neurochemistry
beta 2-Adrenoceptor regulation of CGRP release from capsaicin-sensitive neurons
J. Dent. Res.
Effects of temporomandibular joint stimulation on nociceptive and nonnociceptive neurons of the cat's trigeminal subnucleus caudalis (medullary dorsal horn)
J. Neurophysiol.
Peripheral and central sensitization related to headaches
An association between migraine and cutaneous allodynia
Ann. Neurol.
Dental injury models: experimental tools for understanding neuroinflammatory interactions and polymodal nociceptor functions
Crit. Rev. Oral Biol. Med.
Nociceptors in the orofacial region: Temporomandibular joint and masseter muscle
Evidence that excitatory amino acid receptors within the temporomandibular joint region are involved in the reflex activation of the jaw muscles
J. Neurosci.
Sex-related differences in human pain perception and rat afferent discharge evoked by injection of glutamate into the masseter muscle
J. Neurophysiol
Temporomandibular-evoked jaw muscle reflex: role of brainstem NMDA and non-NMDA receptors
NeuroReport
Activation of peripheral NMDA receptors contributes to human pain and rat afferent discharges evoked by injection of glutamate into the masseter muscle
J. Neurophysiol.
Interstitial glutamate concentration is elevated in the masseter muscle of myofascial temporomandibular disorder patients
J. Orofacial. Pain
Activation of peripheral P2X receptors is sufficient to induce central sensitization in rat medullary dorsal horn nociceptive neurons
NeuroReport, submitted
NMDA receptor mechanisms contribute to neuroplasticity induced in caudalis nociceptive neurons by tooth pulp stimulation
J. Neurophysiol.
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