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Notes: Summary The dura mater encephali of the rat is richly supplied by myelinated (A-axons) and unmyelinated (C-axons) nerve fibres. For the supratentorial part the main nerve supply stems from all three branches of the trigeminal nerve. Finally, 250 myelinated and 800 unmyelinated nerve fibres innervate one side of the supratentorial part. The vascular bed of the dura mater exhibits long postcapillary venules up to 200 μm in length with segments of endothelial fenestration. Lymphatic vessels occur within the dura mater. They leave the cranial cavity through the openings of the cribriform plate, rostral to the bulla tympani together with the transverse sinus, and the middle meningeal artery. The perineural sheath builds up a tube-like net containing the A- and C-axons. It is spacious in the parietal dura mater and dense at the sagittal sinus along its extension from rostral to caudal and at the confluence of sinuses. Terminals of both the A- and C-axons are of the unencapsulated type. Unencapsulated Ruffini-like receptors stemming from A-axons are found in the dural connective tissue at sites where superficial cerebral veins enter the sagittal sinus and at the confluence of sinuses. The terminations of single A-axons together with C-fibre bundles mix up in their final course in one Schwann cell to build up multiaxonal units or terminations (up to 15 axonal profiles). A morphological differentiation is made due to the topography of these terminations; firstly, in different segments of the vascular bed: postcapillary venule, venule, the sinus wall, lymphatic vessel wall, and secondly, within the dura mater: inner periosteal layer, collagenous fibre bundles of the meningeal layer and at the mesothelial cell layer of the subdural space.

Notes: Summary In cats the time course of degeneration following lumbal sympathectomy was studied in the ramus communicans griseus (reg) and in the nerves to the triceps surae muscle using light and electron microscopic methods. The left lumbar sympathetic trunk including its rami communicantes was removed from L2 to S1 using a lateral approach. The animals were sacrificed between 2 and 48 days after the sympathectomy. Tissue samples were taken (a) one cm proximal to the entrance of the rcg into the spinal nerve, and (b) one cm proximal to the entrance of the nerve into the muscle belly. In the reg signs of degeneration can already be recognized in the myelinated as well as in the unmyelinated axons 48h after sympathectomy. The degenerative processes in the axons reach their peak activity at about 4 days p.o. They end a weck later. Signs of the reactions of the Schwann cells and of the endoneural cells can first be seen 2 days p.o. They are most pronounced around the 8th day p.o., and last at least up to the third week. Thereafter the cicatrization processes settled to a rather steady state (total observation period 7 weeks). In the muscle nerves the first signs of an axonal degeneration of the sympathetic fibers can be recognized 4 days after surgery. The signs of axonal degeneration are most striking about 8 days p.o. They have more or less disappeared another week later. The reactions of the Schwann cells also start on the fourth day but outlast the degenerative processes by some 8 days. Thus the degenerative and reactive processes in the reg precede those in the muscle nerves by 2 days early after surgery and by 6 days 3 weeks later. Seven weeks after surgery, fragments of folded basement lamella and Remak bundles with condensed cytoplasm and numerous flat processes are persisting signs of the degeneration. In addition to the differences in time course between the proximal and the distal site of observation, it was also noted that both the axonal degeneration and the reactions of the Schwann cells are more pronounced in the rcg than in the muscle nerve. For example there was abundant mitotic activity in the central endoneural and Schwann cells whereas we could not detect such activity in the periphery. It is concluded that the time course of degeneration and the intensity of the degenerative and reactive processes is, to a considerable extent, determined by the distance between the site of nerve section and the site from which the specimen is taken. Many of the conflicting data in the literature can be explained by this finding.

Notes: Summary In sympathectomized cats the innervation of the Achilles tendon by fine afferent nerve fibers was studied with semithin and ultrathin sections. Several different types of sensory endings of group III and group IV nerve fibers were identified. Of the five different types of endings in the group III range (T III endings), two are located within vessel walls. One of them ends in the circumference of the venous vessels (T III/VV). Its lanceolate terminals have characteristic receptor areas at their edges. The second type ends in the adventitia of lymphatic vessels (T III/LV). Its receptive areas are scattered along their terminal course. Two further group III endings ramify within the connective tissue compartments of the vessel-nerve-fascicles of the peritenonium externum and internum. One type is tightly surrounded by collagen fibrils (T III/PTic); the other terminates between the collagen fiber bundles (T III/PTgc). The latter arrangement recalls the ultrastructural relation between nerve terminals and collagen tissue in Golgi tendon organs. The fifth type innervates the endoneural connective tissue of small nerve fiber bundles (T III/EN). At least some of them come into close contact with bundles of collagen fibers which penetrate the perineural sheath to terminate within the endoneurium. The endings of group IV afferents (T IV endings) show a striking topographic relationship to the blood and lymphatic vessels of all connective tissue compartments of the Achilles tendon. They form penicillate endings which may contain granulated vesicles. In any event, they can easily be discriminated from the T III endings in the vessel walls. In close neighborhood to Remak bundles, a cell has been regularly found which fulfilled all ultrastructural criteria for mast cells. But this cell is not a mast cell proper because it is surrounded by a basal lamina (pseudo mast cell).

Notes: Abstract This study on the effects of capsaicin on primary afferents from normal knee joints of the cat was performed to further elucidate the mechanisms of articular pain evoked by an acute arthritis and by chemical irritants. It showed that close i.a. bolus injection of capsaicin (10−7–10−4 M) excites most fine articular afferents (conduction velocity ≤11.3 m/s) whereas fast units are not excited. Fine afferents with low to medium thresholds to knee joint movement are less readily excited by capsaicin than high threshold ones. The response to capsaicin is usually a rapid burst of impulses of a very short latency. This response pattern differs considerably from that seen after application of endogenous substances produced in inflammation. Thus capsaicin seems to differ in its mode of action from that of endogenous algesic substances.

Notes: Abstract The peripheral and central terminals of primary afferents of the cat's knee joint were studied with light- and electron microscopy (including HRP-transprot methods). The majority of these afferent fibres are unmyelinated or thinly myelinated. In the periphery, they terminate in non-corpuscular endings. A dense network of branching nerve fibres surround the blood vessels to terminate at the vessel walls or in the adjacent dense collagenous tissue. Besides the terminals the fibres show preterminal bulges which are assumed to represent additional transduction sites. This implies that the whole distal fibre portion has a receptive function. The spinal projection is located in lamina I and V–VII of the dorsal horn. This location parallels that of muscular and visceral fibres, pointing to the possibility of a common projection pattern for deep somatic afferent fibres in the spinal cord of the cat.

Notes: Summary 1.Responses were recorded from 160 ascending tract cells in segments L4 to L6 of the spinal cord in chloralose anaesthetized, spinalized cats. The tract cells were identified by antidromic activation following stimulation of pathways in the lateral and ventral funiculi at the level of the spinal cord transection at the thoracolumbar junction. Axonal conduction velocities ranged from 9 to 114 m/s. 2. A sample of 152 of the neurones examined could be subdivided according to the distribution of their receptive fields into 49 cells activated just from receptors located in skin (“s” cells), 17 neurones excited by receptors in deep tissues (“d” cells), 15 units with a convergent input from receptors in skin and deep tissues (“sd” cells), and 25 neurones with a convergent input from the knee joint and either skin (“sj” cells), deep tissues (“dj” cells) or both (“sdj” cells). No receptive fields could be demonstrated for the remaining 46 neurones. 3. “S” and “sj” cells were found almost exclusively in the dorsal horn, whereas many “d”, “sd”, “sdj” and “dj” units were in the ventral horn. Almost all of the cells that lacked receptive fields were in the ventral horn or intermediate grey. 4. Ninety-one of 158 cells (56%) demonstrated no background activity. Of these, 43 cells (27%) lacked receptive fields. Many of the silent neurones were in the ventral horn, but some were in the dorsal horn. Of 25 cells having knee joint input, 18 (72%) had background activity. 5. All of the neurones that had a receptive field in the knee joint also had a convergent input from receptors in other tissues. In 3 cases, there was a receptive field in the skin over the foot (“sj” cells). For 16 cells, receptive fields included not only the knee joint but also skin and deep tissue (“sdj” cells). Usually, the cutaneous receptive field was near the knee joint, but sometimes it was remote, such as on the foot. The deep receptive fields were chiefly in the muscles of the thigh and/or leg. For 6 “dj” cells, the receptive fields included not only the knee joint but also deep fields like those of “sdj” cells. 6. Cutaneous receptive fields were classified as “low threshold” (cells excited best by innocuous intensities of mechanical stimulation), “wide dynamic range” (cells activated by weak mechanical stimuli, but the best responses were to noxious stimuli) or high threshold (innocuous stimuli had little effect, but noxious mechanical stimuli produced a vigorous discharge). Similarly, stimulation of the knee joint with weak mechanical stimuli could excite some neurones, while others could be activated by weak or strong articular stimuli but were excited best by noxious stimuli, and still other neurones were activated by knee joint stimuli only if the intensity was noxious. 7. In several instances, contralateral receptive fields were noted. These were generally in deep tissue or in the knee joint. 8. It was concluded that many of the responses to articular stimulation of the spinal cord ascending tract cells examined in this study could have been mediated by the fine afferent fibres that supply the knee joint. Although further work will be required to determine which particular ascending tracts transmit nociceptive information concerning the knee joint, it can be proposed that many of the responses demonstrated here were likely to play a role in either joint pain of in triggering responses associated with joint pain.

Notes: Summary 1. Recordings were made from 16 ascending tract cells in the spinal cords of anaesthetized, spinalized cats before and after an acute arthritis was produced by injection of kaolin and carrageenan into the knee joint. 2. The responses tested routinely were to passive flexion of the knee, an innocuous movement. In some cases, responses to other movements were also tested, and changes in background discharge rates were monitored. 3. Control recordings for a period of 1 h or in 3 cases of 3 h indicated that the responses to flexion were reasonably stationary. 4. Four tract cells that initially showed little or no response to flexion of the knee joint developed large responses within 1 to 2 h after inflammation of the joint. 5. Another 9 cells were tested that had responses to flexion of the knee joint prior to inflammation. In 6 cases, inflammation produced enhanced static or transient responses. In 2 cases, the effect of flexion was initially inhibitory or variable, but after inflammation these cells showed large excitatory responses. In the other case, inflammation had no effect. Background discharges were increased by inflammation in 6 of these 9 cells. 6. The effect of inflammation of the knee joint was tested on 3 tract cells that had no clearly defined receptive field in the knee. In 1 case, a response developed to knee flexion after acute inflammation was produced. In the other 2 cases, there were initially responses to knee flexion, but these were unchanged by inflammation. 7. Two of the cells tested had bilateral receptive fields in or around the knee joints. Inflammation of one knee joint enhanced the responses to flexion of the same but not of the contralateral knee in one case but greatly increased the responses to flexion of both knees in the other case. 8. Injections of prostaglandin (PGE2) caused an enhancement of the responses to knee flexion beyond that caused by inflammation in 5 of 7 cases. One cell whose responses to flexion of the knee were unaffected by inflammation showed inhibitory responses to prostaglandin injections into the inflamed knee joint. 9. The effects of inflammation on the responses of ascending tract cells of the spinal cord appear to serve as a useful neural model of the events responsible for the development of arthritic pain.

Notes: Abstract In 18 cats anaesthetized with alpha-chloralose, we recorded from thin myelinated and unmyelinated articular afferents of the medial articular nerve of the knee joint. Bradykinin was injected intra-arterially close to the knee, alone and in combination with prostaglandin E2 (PGE2), and changes of the responses of single afferents to movements of the knee were monitored. Bradykinin changed the mechanosensitivity in 20 of 28 afferents inducing movement sensitivity in initially unresponsive units, lowering the threshold for movements in high-threshold afferents and/ or enhancing pre-existing responses to innocuous and/or noxious joint movements in low and high threshold units. Also the application of PGE2 and bradykinin within a short interval sensitized the majority of these afferents, and in about 50% of the afferents the effect of the combination was superior to those induced by the single substances. We conclude that the inflammatory mediator bradykinin is able to sensitize articular afferents for movement stimuli and that PGE2 may enhance this effect. It is suggested that in arthritis inflammatory mediators act synergistically in the initiation and stabilization of the increased mechanosensitivity of slowly conducting articular afferents.