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Notes: Abstract Electrophysiological experiments in anesthetized cats and rats were performed in order to study the effects of dipyrone on single afferent fibers from the knee joint and on spinal cord neurons with knee joint input. The neurons were activated and/or rendered hyperexcitable by an acute inflammation in the knee joint. In the joint nerve in cats, intravenous dipyrone (25–100 mg/kg) reduced ongoing activity in 10/12 thinly myelinated afferents but only in 1/10 unmyelinated afferents; the responses to movements of the inflamed knee were reduced in 8/10 thinly myelinated but only in 3/10 unmyelinated units. The reduction of activity was significant 20–30 min after application and was maximal at 60–180 min. In the spinal cord of spinalized cats, intravenous dipyrone (25–100 mg/kg) reduced ongoing activity and/or responses to pressure onto the inflamed knee in 14/16 neurons and in non-spinalized rats similar effects were seen in 10/11 neurons. Effects on spinal cord neurons started 5–10 min after application and were maximal after 20–40 min. These data show pronounced suppression of inflammation-induced nociception by dipyrone and they suggest that the spinal cord is a major site of action of this compound.

Notes: Summary In five types of mechanoreceptor afferents of the cat's hind foot, the primary afferent depolarization (PAD) induced by mechanical skin stimulation was measured by testing the excitability of their terminations in the dorsal horn. Two types of skin stimuli were used to set up activity in distinct populations of rapidly and slowly adapting mechanoreceptors respectively. The experiments revealed that two systems exist to generate PAD in cutaneous afferents, both being of negative feedback character. One system is activated by impulses from rapidly adapting low threshold receptors and preferentially depolarizes the terminals of such afferents, and correspondingly, the other system is activated by and operates on the slowly adapting units. In both PAD systems the size of the depolarization is graded depending on the stimulus strength. Further, the “tonic” system displays a “surround” pattern of organization similar to that of the “phasic” system which has already been described (Schmidt et al. 1967b). In the discussion the operational relationships of both systems and their functional implications are outlined.

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: 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 In ten cats, single unit electrical activity was recorded in the lumbosacral spinal cord from neurones driven by stimulation of afferent fibres from the ipsilateral knee joint. Tonic descending inhibition (TDI) on the responses of these cells was measured as increases in resting and evoked activity of the neurones following reversible spinalization of the animals with a cold block at upper lumbar level. Acute inflammation of the knee joint was induced in five of the cats by the injection of kaolin and carrageenan into the joint. TDI was observed in 25 of 33 neurones recorded in normal animals (76%) and in 36 of 40 (90%) neurones recorded in animals with acute knee joint inflammation. In both kinds of preparation TDI was more pronounced in neurones recorded in the deep dorsal horn and in the ventral horn than in those recorded in the superficial dorsal horn. There was a tendency in the whole sample for TDI to be greater in neurones with input from inflamed knees. We conclude that the spinal processing of afferent information from joints is under tonic descending influences and that the amount of TDI can be altered during acute arthritis.