Pain, 51 (1992) 241-247 0 1992 Elsevier Science Publishers B.V. All rights reserved 0304-3959/92/$05.00 241 PAIN 02161 P-Endorphin processing and cellular origins in rat spinal cord Howard B. Gutstein, David M. Bronstein and Huda Akil Department of Anesthesiology and Mental Health Research Institute, University of Michigan, Ann Arbor, MI (USA) (Received 7 February 1992, revision received 24 June 1992, accepted 26 June 1992) Summary While enkephalin and dynorphin peptides have been well characterized in the spinal cord, the cellular localization of P-endorphin (PE) and the processing of pro-opiomelanocortin (POMC) to j3E and other non-opioid peptides in the cord have not been extensively investigated. Other investigators have characterized the various PE forms present in rat spinal cord regions. Previous studies have also suggested that spinal POMC content is entirely derived from supraspinal sources. However, high proportions of /3E precursors present in spinal cord sieving profiles led us to suspect the presence of POMC cell bodies intrinsic to the cord. In this study, we performed thoracic spinal cord lesions on a group of animals and demonstrated the persistence of about one-third of control levels of /3E immunoreactivity (PE-IR) below the level of the lesions. We also characterized POMC processing in various regions of the spinal cord both before and after lesioning. These data suggested that there may be intrinsic POMC/endorphinergic neuronal systems in the spinal cord. Key words: Pro-opiomelanocortin; p-Endorphin; Spinal cord; Peptide processing Introduction Pain research has increasingly focused on the role of the spinal cord in the modulation and processing of nociceptive inputs. Part of this attention has been focused on the possible role of opioid peptides, in particular enkephalin and dynorphin, in modulating nociceptive inputs from primary afferent fibers in the dorsal horn of the cord (Cruz and Basbaum 1985; Iadarola et al. 1988a,b). Enkephalin may provide an evanescent analgetic effect because of its rapid degra- dation after release (Frederickson et al. 1981; Holaday 1985). Dynorphin has been shown to modulate certain types of pain at kappa receptors. However, it has also been shown to have no analgetic effect and antagonis- tic non-opioid effects (Tung and Yaksh 1982; Walker et al. 1982a,b). In spite of the fact that /3-endorphin (PE) in its unacetylated, 31 amino acid form, is one of the most potent endogenous analgetic compounds (Bradbury et al. 1976; Deakin et al. 19801, little re- Correspondence to: Howard B. Gutstein, M.D., Section of Pedi- atric Anesthesiology, C.S. Mott Children’s Hospital (C-41391, Box 0800, Ann Arbor, MI, 48109-0800, USA. search has been done to determine whether this pep- tide is important in the control of nociception at the spinal level. PE has been shown to play important roles in stimulation-produced analgesia, stress-induced analgesia, and in supraspinal modulation of nociceptive input (Akil 1982). While immunohistochemical data (Tsou et al. 1986) first revealed the presence of PE immunoreactivity (PE-IR) in the cord, the potential involvment of this opioid in spinal pain processing could not be ascertained without a better appreciation of the origins and molecular forms of this immunoreac- tivity (IR). BE is differentially processed in regions of the CNS to opioid active, inactive, and antagonistic forms (Zakarian and Smyth 1979; Akil et al. 1981; Chretien et al. 1984; Hammonds et al. 1984). It is possible that each of these forms, or perhaps the relative ratios of these forms present at a synapse, could be important in the modulation of nociceptive information. PE is derived from pro-opiomelanocortin (POMC), 1 of 3 known endogenous opioid peptide precursors. Its anatomic distribution in the CNS and pituitary appears to be more discrete than that of other endoge- nous opioids, cell bodies being localized to the anterior and intermediate lobes of the pituitary, the arcuate