Neurotransmitters released by nociceptive afferents that activate spinothalamic tract cells include the excitatory amino acid glutamate and any of several peptides, such as SP, CGRP, and vasoactive intestinal polypeptide (VIP). Glutamate appears to act as a fast transmitter by its action on non-NMDA excitatory amino acid receptors. However, with repetitive stimulation, glutamate can also act through NMDA receptors. Peptides appear to act as neuromodulators. For example, through a combined action with an excitatory amino acid such as glutamate, SP can produce a long-lasting increase in the responses of spinothalamic tract cells; this enhanced responsiveness is called central sensitization. CGRP seems to increase release of SP and prolong the action of SP by inhibiting its enzymatic degradation.
Spinothalamic tract cells often have inhibitory receptive fields. Inhibition may result from weak mechanical stimuli, but usually the most effective inhibitory stimuli •Fig. 7.7 A,Responsesofawide–dynamicrangeormultireceptivespinothalamictractcell.B,Responsesofahigh-thresholdspinothalamictractcell.Graphsshowresponsestogradedintensitiesofmechanicalstimulation.Brushstimulusisacamel’shairbrushrepeatedlystrokedacrossthereceptivefield.Pressureisappliedbyattachmentofanarterialcliptotheskin.Thisisamarginallypainfulstimulustoahuman.Pinchisachievedbyattachmentofastiffarterialcliptotheskinandisdistinctlypainful.Squeezeisappliedbycompressingafoldofskinwithforcepsandisdamagingtotheskin.
are noxious ones. The nociceptive inhibitory receptive fields may be very large and may include most of the body and face. Such receptive fields may account for the ability of various physical manipulations, including transcutaneous electrical nerve stimulation and acupuncture, to suppress pain. Neurotransmitters that can inhibit spinothalamic tract cells include the inhibitory amino acids GABA and glycine, as well as monoamines and the endogenous opioid peptides.
Spinoreticular tract neurons frequently have large, sometimes bilateral receptive fields, and effective stimuli include noxious ones. These dorsal horn neurons target multiple regions in the medullary and pontine reticular formation. The reticular formation, which projects to the intralaminar complex of the thalamus and thereby to wide areas of the cerebral cortex, is involved in attentional mechanisms and arousal (see
Chapter 10).
The reticular formation also gives rise to descending reticulospinal projections, which contribute to the descending systems that control transmission of pain.
Many cells of the spinomesencephalic tract respond to noxious stimuli, and the receptive fields may be small or large. The terminations of this tract are in several midbrain nuclei, including the periaqueductal gray, which is an important component of the endogenous analgesia system. Motivational responses may also result from activation of the periaqueductal gray matter. For example, stimulation in the periaqueductal gray matter can cause vocalization and aversive behavior. Information from the midbrain is relayed not only to the thalamus but also to the amygdala. This provides one of several pathways by which noxious stimuli can trigger emotional responses.