Ascending nociceptive pathways
Slides from Willis and Westlund 1997
1. anterolateral system (spinothalamic tract) - The spinothalamic tract in humans is believed to help mediate the sensations of pain, cold, warmth, and touch - In monkeys, a large fraction of spinothalamic tract cells is located in the lumbar and sacral enlargements, and these cells are concentrated in the marginal zone and neck of the dorsal horn in laminae I and IV-VI (Fig. 6) (Willis et al., 1979; Apkarian and Hodge, 1989a). However, some spinothalamic cells are located in other laminae, including lamina X, which is around the central canal, and in the ventral horn. Comparison of the populations of spinothalamic tract cells projecting to the lateral thalamus, including the ventral posterior lateral nucleus, and those projecting to the medial thalamus, including the central lateral nucleus, show clear differences between the two (Willis et al., 1979). - The projections of the spinothalamic tract have been traced to the thalamus in humans - Primate spinothalamic tract cells that project to the region of the CL nucleus in the medial thalamus may also collateralize to the lateral thalamus (Fig. 6); these cells have response properties identical to those of spinothalamic tract cells that project just to the lateral thalamus (Giesler et al., 1981). - Spinothalamic tract cells have not only excitatory but also inhibitory receptive fields (Gerhart et al., 1981b). The strongest inhibition from stimulation of the skin occurs when noxious intensities of stimulation are used, suggesting that a mechanism similar to DNIC is involved.
2. spinomesecephalic tract - The cells of origin of the spinomesecephalic tract are distributed in the spinal cord in a manner similar to that of the cells of origin of the spinothalamic tract. - The spinomesencephalic projections are to the following midbrain nuclei: periaqueductal gray, nucleus cuneiformis (Fig. 8), intercolliculus nucleus, deep layers of the superior colliculus, nucleus of Darkschewitsch, anterior and posterior pretectal nuclei, red nucleus, Edinger-Westphal nucleus, and interstitial nucleus of Cajal. - Spinomesencephlic neurons are nociceptive, responding either to noxious stimuli only or best to noxious but also to innocuous stimuli - The different components of the spinomesencephalic tract may have different functions; e.g., the projections to the periaqueductal gray(PAG) could contribute to aversive behavior (Skultety, 1963; Nashold et al., 1969) as well as activate the descending analgesia system that arises from the PAG (described below). The projections to the nucleus cuneiformis could access the midbrain locomotor center (see Brooks, 1986) and the ascending reticular activating system (Magoun, 1963). Input to the deep layers of the superior colliculus are likely to play a role in orienting. Because the anterior pretectal nucleus is another locus that produces analgesia when stimulates (Rees and Roberts, 1993) (described below), the projections here may serve to limit nociception.
3. spinoreticular tracts - Many of the cells of origin of the spinoreticular tracts are located in the deep layers of the dorsal horn and in laminae VII and VIII of the ventral horn. - The spinoreticular projections to the caudal medulla end in several nuclei, including the retroambiguus and superspinalis nuclei as well as dorsal and ventral parts of the nucleus medullae oblongatae centralis (Mehler et al., 1960). More rostral projections are to the lateral reticular nucleus, the nucleus gigantocellularis (Fig. 9), the nuclei paragigantocellularis dorsalis and lateralis, and the nuclei pontis caudalis and oralis. - Another major termination of spinoreticular fibers in the brainstem is in the parabrachial region - Many reticular neurons respond preferentially to noxious stimuli (Wolstencroft, 1964; Casey, 1969, 1971a; Guilbaud et al., 1973; Foote et al., 1991). The primary functional significance of this input is undoubtedly to signal homeostatic changes to brainstem autonomic centers, but other brainstem responses include activation of endogenous analgesia systems and relay of information that triggers motivational-affective responses.
4. spino-limbic tracts - A multisynaptic pathway is proposed as the means of carrying information about noxious inputs to the medial thalamus, where it is relayed to the limbic system(Bishop, 1959); this is sometimes termed the spinoreticulothalamic pathway. - Ascending projections from the reticular formation have been reported to the medial thalamus, hypothalamus, and limbic structures - In addition, direct spinohypothalamic (Burstein et al., 1987, 1990) and spinoamygdalar (Bernard and Besson, 1990; Burstein and Potrebic, 1993; Menétrey and de Pommery, 1991) pathways have been described. - Some spinal projections also innervate the nucleus accumbens and the septal nuclei, suggesting that a component of this pathway is relevant to the motivational aspects of pain (Burstein and Giesler, 1989). - The spinopontoamygdalar pathway (Bernard and Besson, 1990; Menétrey and de Pommery, 1991; Burstein and Potrebic, 1993) arises from cells situated bilaterally in the lateral reticulated area of the deep dorsal horn and in the gray matter surrounding the central canal. Anterograde tracing studies indicate that the central nucleus of the amygdala is directly innervated innervated by terminals arising from the spinal cord (Fig. 12)(Cliffer et al., 1991).
Dorsal Quadrant 5. Spinocervicothalamic Pathway - The spinocervicothalamic pathway originates from neurons in the spinal cord dorsal horn and relays in the lateral cervical nucleus in segments C1 and C2. - The axons of spinocervical tract neurons ascend in the dorsal part of the lateral funiculus to the upper cervical level (Nijensohn and Kerr, 1975) and then terminate in the lateral cervical nucleus. - Many spinocervical tract cells have tactile responses and thus would not be candidates for a nociceptive role. However, some spinocervical tract cells do respond to noxious stimuli.
6. postsynaptic dorsal column pathway - The postsynaptic dorsal column pathway arises from cells distributed medial to laterally in lamina III in the dorsal horn, as well as from a few cells just lateral to lamina X (Fig. 13)(Rustioni, 1973, 1974; Rustioni et al., 1979; Bennett et al., 1983; Giesler et al., 1984). The postsynaptic dorsal column cells, in contrast to spinothalamic tract cells, are innervated by “serotonin-only” fibers, meaning that no coexisting peptide content could be identified in the serotonin-containing synapses(Wu and Wessendorf, 1992).
