Recent Publications by CFE Educators

Immunocytochemical analysis of the distribution of dynorphin B terminals in the sacral spinal cord of the cat revealed a pattern of staining very similar to that produced with antisera directed against the primary afferent derived, putative neurotransmitter, vasoactive intestinal polypeptide. Labeled axons and terminals were concentrated in lamina I and V and there was dense fiber staining in the tract of Lissauer. Of particular interest was the presence of immunoreactive axons in attached dorsal rootlets. To specifically focus on the possibility that some of the sacral primary afferent fibers are dynorphin-immunoreactive, we first tried to increase perikaryal labeling in the sacral dorsal root ganglia by topical treatment with colchicine. This did not produce immunoreactive labeling of cell bodies in the ganglia. Unilateral multiple dorsal rhizotomy (L5 to coccygeal 1), however, significantly decreased the staining of dynorphin-immunoreactive axons and terminals in the tract of Lissauer and in the dorsal horn of sacral segments ipsilateral to the deafferentation. No changes were detected in the lumbar cord. Finally, radioimmunoassay of caudal lumbar and sacral dorsal root ganglia was performed. Measurable immunoreactivity was found in all ganglia assayed, but, consistent with the histochemical analysis, sacral ganglia contained the highest concentration of immunoreactive dynorphin B. These data indicate that a significant component of the sacral spinal cord dynorphin terminal immunoreactivity derives from primary afferent fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophysiological and immunocytochemical techniques were used in the abdominal ganglion of Aplysia to identify neurons containing immunoreactive FMRFamide. Large numbers of neurons were immunoreactive for FMRFamide, including R2, L2, L3, L4, L5, L6, 2 cells tentatively identified as L12 and L13, and a previously unidentified cluster on the ventral surface of the right lower quadrant. There was also heavy labelling of fibers, often with beaded varicosities, throughout the neuropil, the cell layers, and the sheath overlying the ganglion. This data provides further evidence that FMRFamide is an important neurotransmitter in Aplysia. The demonstration of immunoreactive FMRFamide in the giant cholinergic neurons R2 and LP1(1) suggests that these well-studied and experimentally convenient cells use acetylcholine and an FMRFamide-like peptide as cotransmitters.

Monitoring the quality of well-established multisite clerkships can be aided by the use of trend analysis and graphic-oriented presentations. Five years of data on student performance, experience, and perceptions are reported for an obstetrics and gynecology clerkship offered at eight geographically dispersed sites. Of the five measures of student performance, two (final written and oral examinations) showed major changes. Trends also appeared in student participation in deliveries and student ratings of teaching over time. The results of these analyses were communicated to faculty at each site and used to make improvements in the clerkship. The implications and use of these longitudinal evaluation procedures are discussed.

Using immunocytochemistry, we have identified important differences in the distribution of immunoreactive dynorphin and enkephalin cells and terminals in the trigeminal nucleus caudalis and in the spinal dorsal horn of the cat. Dynorphin immunoreactive processes are more closely associated with those regions of cord that process nociceptive information, specifically laminae I and V. Enkephalin neurons and terminals are more widespread. Based on the staining pattern with an antiserum to the octapeptide-metenkephalin-arg-gly-leu, we suggest that the dense enkephalin terminal immunoreactivity in the inner part of the substantia gelatinosa derives from cells in lamina III. There are also significant differences in the anatomical relationship of the two opioid peptides with the organization of parasympathetic autonomic preganglionic neurons. The functional significance of these observations must await physiological analysis; nevertheless, it is almost certain that differences will be found and that these will be important in understanding the mechanisms through which exogenous opiates and a variety of descending control systems exert their effects on spinal cord neurons.

The release of the peptide neurotransmitter substance P from the peripheral terminals of nociceptive afferent neurons and the release of catecholamines from postganglionic sympathetic efferent neurons produce physiologic changes associated with acute inflammation. The contribution of these neurogenic mechanisms to inflammatory diseases has not been determined. Activation of central neural circuits elicits similar physiologic changes, and lesions of the peripheral and central nervous system are associated with alteration in activity of inflammatory diseases. We have evaluated the contribution of neurogenic inflammation to the severity of joint injury in experimentally induced arthritis in the rat. The finding of a greater density of substance P-containing nociceptive afferents in a joint that develops more severe arthritis (ankle) suggests a role of substance P in joint injury. Direct evidence that the proinflammatory factor released from these nociceptors is substance P is provided by the finding that the injection of substance P into a joint which normally develops less severe arthritis (knee) increases the severity of arthritis in that joint. A contribution of catecholamines to the severity of joint injury was suggested by the finding that both guanethidine-induced sympathectomy and reserpine-induced depletion of catecholamines attenuated the severity of joint injury. Finally, a contribution of central neural circuits to inflammatory processes was studied in a model in which activation of nociceptive afferents elicited swelling and tenderness at a remote site. This reflex neurogenic inflammation was inhibited by intracerebroventricular injections of morphine, which also attenuated the severity of arthritis. These studies provide evidence that elements of the peripheral afferent and sympathetic efferent neurons and of descending supraspinal, opioid-mediated, circuits in the central nervous system modulate the severity of joint injury in experimental arthritis in the rat.

No current theory of the mechanisms involved in the pathophysiology of rheumatoid arthritis (RA) explains its important clinical features. We hypothesize that neural mechanisms are involved in this pathophysiology and they explain at least 3 clinical features: specific high risk joints are more likely to develop arthritis; specific high risk joints have more severe arthritis; and RA is bilaterally symmetric. If our hypothesis is correct, it will provide a rationale for the development of new therapies for what is now an inadequately treated disease.

Recent studies of the mechanism of neurogenic inflammation have focused on the contribution of neuropeptides released from peripheral terminals of primary afferent sensory neurons. In this study we addressed the contribution of humoral and neural factors to the hyperalgesia and swelling that are produced contralateral to an injured hindpaw, a phenomenon which we refer to as reflex neurogenic inflammation. The contralateral inflammatory response develops gradually, over a period of hours, and shows no tachyphylaxis with repeated application of the same stimulus. Denervation of either limb significantly attenuated the contralateral responses. Selective lesions of small-diameter, presumed nociceptive afferent fibers with capsaicin, or of sympathetic postganglionic efferents by immunosympathectomy, also reduced swelling and hyperalgesia of the uninjured paw. Interruption of venous circulation to the injured limb by vein ligation did not alter the response in the contralateral paw. Taken together, these data suggest that reflex neurogenic inflammation is neurally mediated, via connections across the spinal cord.