Peripheral and central mechanisms of orofacial inflammatory pain

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Abstract

Many orofacial pain conditions involve inflammation of orofacial tissues and they range from acute pulpitis (toothache) and mucositis to chronic arthritic conditions affecting the temporomandibular joint (TMJ). This article reviews the peripheral and central neural mechanisms involved in orofacial inflammatory pain states, including the integral role that peripheral and central sensitization play in the pain features that characterize these states. It also outlines the recent evidence for the contribution of non-neural processes, especially those involving glial cells.

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

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