Use of epidural steroids for treatment of arthritic pain

$230 PEPTIDES AND PAIN PATHWAYS. T. Hdkfelt and J.M. Lundberg, 282 Plen Department of Histology, Karolinska I n s t i t u t e t , Stockholm, Fridoy Sweden. Neuroanatomical and physiological investigations have during the years provided extensive knowledge of the pathways involved in pain mechanisms. Much less is known about the chemical c h a r a c t e r i s t i c s of these systems, such as the type of transmitter released from these neurons. Recent advances in enzyme and peptide biochemistry, as well as the application of s p e c i f i c histochemical techniques, p a r t i c u l a r l y immunohistochemistry, have provided some preliminary insight into this issue. Already in 1953 Lembeck (Naunyn-Schmiedeberg's Arch. 219, 197, 1953) suggested that substance P, a compound discovered by von Euler and Gaddum (J. Physiol. 72, 74, 1931), could be transmitter in primary sensory neurons. The s t r u c ~ ral characterization of substance P as an undecapeptide (Chang et a l . , Nature 232, 86, 1971) formed a basis for the elegant electrophys-fo~gical s t u d i e s ~ O t s u k a and collaborators (Otsuka and Takahashi, Rev. Pharmac. Tox. 17, 425, 1977), strongly suggesting a transmitter role for substance P released from primary sensory neurons in the spinal cord. The immunohistochemical analysis revealed that substance P-like immunoreactivity was present in a population of primary sensory neurons, p r e f e r e n t i a l l y of the small type (B-type). Furthermore, f i b r e s containing t h i s peptide were found both in the spinal cord as well as in various peripheral tissues, including skin, and transection of the dorsal roots markedly decreased the number of these f i b r e s in the s u p e r f i c i a l laminae of the dorsal horn. However, also other peptides are present in primary sensory neurons. Thus, a somatostatin-like peptide could be visualized in a small population of spinal ganglion c e l l s . These c e l l s were exclusively of the small type. Subsequently also a cholecystokinin (CCK)-like peptide, as well as a vasoactive i n t e s t i n a l polypeptide ( V I P ) - l i k e peptide could be demonstrated in primary sensory neurons. The proportion of the peptide containing c e l l s seem to vary between d i f f e r e n t species. In the guinea-pig, VIP neurons are most numerous, whereas in the rat substance P neurons seem to constitute the largest population. In primary sensory neurons in rat all four peptides are affected by capsaicin treatment (Jancs6 et a l . Neuroscience, in press). In addition to primary sensory a f f e r e n t s , there are also peptide f i b r e s in the dorsal horn, which have a central o r i g i n . Thus, enkephalin, neurotensin (Uhl et a l . , Brain Res. 167, 77, 1979), substance P and avian pancreatic poly~pt-Tde (APP) immunoreactive cell bodies have been observed in the dorsal horn of the spinal cord. Furthermore, a small group of enkephalin immunoreactive neruons projecting to the spinal cord have been observed in the pars of the nucleus g i g a n t o c e l l u l a r i s in the medulla oblongata. Also substance P neurons may descend from the medulla oblongata to the dorsal horn. Some of these neurons may contain both substance P and 5-hydroxytryptamine. F i n a l l y , angiotensin I I (Fuxe et a l . , Neurosci. Letts. 2, 229, 1976) and neurophysin immunoreactive f i ~ e s - o r i ginating in the paraventricular nucleus also seem to innervate the dorsal horn (Swanson, Brain Res. 128, 356, 1977). In conclusion, using immunohistochemical techniques d i f f e r e n t types of peptides have been demonstrated in primary sensory neurons, local spinal neurons as well as in supraspinal descending systems. To what extent these systems are involved in pain mechanisms and, i f so, what role these peptides play, remains to be elucidated.