Spinothalamic tract cells are activated by neurotransmitters released by nociceptive afferents. These include glutamate, an excitatory amino acid, and several peptides such as SP, CGRP, and VIP. Glutamate acts as a fast transmitter through non-NMDA excitatory amino acid receptors and can also act through NMDA receptors with repetitive stimulation. Peptides function as neuromodulators and can enhance the responsiveness of spinothalamic tract cells when combined with glutamate, a process known as central sensitization. CGRP increases the release of SP and inhibits its enzymatic degradation, prolonging its action.

In addition, spinothalamic tract cells have inhibitory receptive fields. Inhibition can occur due to weak mechanical stimuli but is more effective with noxious stimuli. These inhibitory receptive fields can be large, covering most of the body and face. This may explain why physical manipulations like transcutaneous electrical nerve stimulation and acupuncture can suppress pain. Neurotransmitters such as GABA, glycine, monoamines, and endogenous opioid peptides can also inhibit spinothalamic tract cells.

Spinoreticular tract neurons have large, sometimes bilateral receptive fields, and they respond to noxious stimuli. These neurons target various regions in the medullary and pontine reticular formation. The reticular formation is involved in attentional mechanisms and arousal and projects to the intralaminar complex of the thalamus, which then relays information to wide areas of the cerebral cortex. The reticular formation also sends descending reticulospinal projections that contribute to pain transmission control.

The spinomesencephalic tract consists of cells that respond to noxious stimuli, and their receptive fields can be either small or large. This tract terminates in several midbrain nuclei, including the periaqueductal gray, which is important for the endogenous analgesia system. Activation of the periaqueductal gray can elicit vocalization and aversive behavior. The midbrain also relays information to the thalamus and amygdala, providing pathways for noxious stimuli to trigger emotional responses.
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.