Neural mechanisms and pathways in craniofacial pain.

Many free nerve endings of small-diameter afferents (A-delta or C nerve fibres) respond to craniofacial noxious stimuli and a number of neurochemicals are involved in their activation or sensitization. The small-diameter nociceptive afferents project to the trigeminal (V) brainstem complex where they can excite nociceptive neurones that have been categorized as either nociceptive-specific (NS) or wide dynamic range (WDR). These neurones project to other brainstem regions or to the contralateral thalamus. The lateral and medial thalamus contain NS and WDR neurones which have properties and connections with the overlying cerebral cortex or other thalamic regions indicative of a role for most of them in the sensory-discriminative, affective or other dimensions of pain. Some of the V brainstem NS and WDR neurones respond exclusively to cutaneous sensory inputs and have features indicating their involvement in acute superficial craniofacial pain. Many of the neurones, however, receive convergent inputs from afferents supplying other craniofacial tissues (e.g. cerebrovascular, muscle) as well as skin, and are likely involved in deep pain, as well as spread and referral that is typically seen in headache and several craniofacial pain conditions involving deep tissues. Convergence may also be an important factor underlying the neuroplastic changes in V neuronal properties that may occur with peripheral injury or inflammation. These changes include a prolonged enhancement of the cutaneous as well as deep afferent inputs to most NS and WDR neurones and expansion of their cutaneous or deep mechanoreceptive field and increased EMG activity in the jaw musculature. They involve NMDA, non-NMDA and opioid neurochemical mechanisms within peripheral tissues as well as within the CNS. Such modulatory effects on brainstem neuronal properties reflect the functional plasticity of the central V system, and may be involved in the development of headache and other conditions that manifest craniofacial pain.