Spinal dorsal horn

Afferent input from cutaneous and visceral nociceptors is known to converge on spinal neurons, which accounts for the referral of pain between visceral and cutaneous structures (e.g. cardiac pain gets referred to the chest and left upper arm in patients suffering from angina pectoris). Projection neurons in the spinal dorsal horn project to cell nuclei in supraspinal areas such as the thalamus, brainstem and midbrain. Of these, the synaptic junctions in the thalamus play a very important role in the integration and modulation of spinal nociceptive and non-nociceptive inputs. Nociceptive inputs are finally conducted to the cortex where the sensation of pain is perceived (Fig. 1). The mechanisms via which the cortex processes nociceptive inputs are only poorly understood. 

Snznki R, Matthews EA, Dickenson AH (2001) Comparison of the effects of MK-801, ketamine and memantine on responses of spinal dorsal horn nenrones in a rat model of mononenropathy. Pain 91 101-109... 

Murasaki M, Mori A, Endo S, et al Late phase 2 study of a new anxiolytic SM-3997 (tandospirone) on neurosis. Clinical Evaluation 20 259-293, 1992 Murase K, Randic M, Shirasaki T, et al Serotonin suppresses N-methyl-D-aspartate responses in acutely isolated spinal dorsal horn neurones of the rat. Brain Res 525 84-91, 1990... 

PGI2, and PGF2e, contribute to so-called central sensitization, an increase in excitability of spinal dorsal horn neurons, that augments pain intensity, widens the area of pain perception, and results in pain from innocuous stimuli. 

Opioid-induced antinociception depends, to some degree, on monoaminergic signaling in the spinal dorsal horn. While opioids can act directly on dorsal horn terminals of primary afferent nociceptive fibers or on excitatory interneurons in lamina II of the dorsal horn to reduce the release of excitatory transmitters (Glaum et al., 1994), the supraspinally mediated analgesic effects of opioids, at least in part, involve interactions with central and spinal serotonergic and noradrenergic transmission. 

Azkue, J..J., Murga, M., Fernandez-Capetillo, O., Mateos, J. M., Elezgarai, I., Benitez, R., Osorio, A., Diez, J., Puente, N., Bilbao, A., Bidaurrazaga, A., Kuhn, R., Grandes, P.. Immunoreactivity for the group III metabotropic glutamate receptor subtype mGluR4a in the superficial laminae of the rat spinal dorsal horn. J. Comp. Neurol. 2001, 430, 448-57. 

The striatum, the nucleus accumbens, the hippocampus, the lateral nucleus of the hypothalamus, the habenula, the interpeduncular nucleus, the nucleus of the tractus soli-tarius, the raphe nuclei and the medulla oblongata are rich in tachykinin NK1 receptors (Otsuka and Yoshioka, 1993). The predominant expression of N receptors within the spinal dorsal horn is consistent with the assumption that SP and NKA are important messengers here (Bleazard et al., 1994). The distribution of NKi receptors in the peripheral nervous system and in the gut are discussed elsewhere (McLean, 1996 Quartara and Maggi, 1997, 1998). 

Radhakrishnan, V., Iyengar, S., Henry, J.L. The nonpeptide NK1 receptor antagonists LY303870 and LY306740 block the responses of spinal dorsal horn neurons to substance P and to peripheral noxious stimuli, Neuroscience 1998, 83, 1251-1260. 

Radhakrishnan, V. and Henry, J. L. Novel substance P antagonist, CP-96345, blocks responses of cat spinal dorsal horn neurons to noxious cutaneous stimulation and to substance P, Neurosci. Lett. 1991, 132, 39-43. 

Nitric oxide inhibition has an analgesic effect in patients with chronic tension-type headache, probably due to a reduction in central sensitization at the level of the spinal dorsal horn, trigeminal nucleus or both (Ashina, 2002). 

Lappin SC, Randall AD, Gunthorpe MJ, Morisset V (2006) TRPV1 antagonist, SB-366791, inhibits glutamatergic synaptic transmission in rat spinal dorsal horn following peripheral inflammation. Eur J Pharmacol 540 73... 

The medial thalamic neurons receive the projection arising from the spinal dorsal horn through the spino-thalamic tract and then project to cortical structures, including the ACC. Wang et al. (2007) used a CPA paradigm to examine the... 

Wei, X. H, Zang, Y., Wu, C. Y, Xu, J. T, Xin, W. J., and Liu, X. G. (2007). Peri-sciatic administration of recombinant rat TNF-alpha induces mechanical allodynia via upregulation of TNF-alpha in dorsal root ganglia and in spinal dorsal horn The role of NF-kappa B pathway. 

Weng, H. R., Cordelia, J. V., and Dougherty, P. M. (2003). Changes in sensory processing in the spinal dorsal horn accompany vincristine-induced hyperalgesia and allodynia. Pain 103, 131—138. White, F. A., Jung, H., and Miller, R. J. (2007). Chemokines and the pathophysiology of neuropathic pain. Proc.. Natl. Acad. Sci. USA 104, 20151—20158. 

Gao, X., Kim, H. K., Chung, J. M., and Chung, K. (2005). Enhancement of NMDA receptor phosphorylation of the spinal dorsal horn and nucleus gracilis neurons in neuropathic rats. Pain 116, 62-72. 

Ma, W., and Quirion, R. (2002). Partial sciatic nerve ligation induces increase in the phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) in astrocytes in the lumbar spinal dorsal horn and the gracile nucleus. Pain 99, 175-184. 

Yasaka T, Kato G, Furue H, Rashid MH, Sonohata M, et al. 2007. Cell-type-specific excitatory and inhibitory circuits involving primary afferents in the substantia gela-tinosa of the rat spinal dorsal horn in vitro. J Physiol 581 603-618. 

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