Response pattern of visceral afferent fibres,supplying the colon,upon chemical and mechanical stimuli

In the cat responses of afferent fibres in the inferior splanchnic nerves which innervate the colon and its mesentery were investigated upon intra-arterial bolus injection of bradykinin, of KCl- and of hypertonic NaCl-solution and upon ischaemia of the colon. One hundred and twenty-five units were analyzed. 1) Seventy-seven from 96 units with resting activity (80%) and 7 from 29 units without (24%) were excited by bradykinin. The exictation was present both when the colon wall contracted and when the contractions were prevented or when the colon was paralytic. 2) Fifty-two from 82 units with resting activity (67%) and 4 from 21 units without (19%) responded to KCl with short-lasting, high-frequency bursts. Injections of hypertonic NaCl-solutions had only small effects on the afferent units. 3) The responses of the units to distension of the colon (see [3]) and to the chemical stimuli were highly correlated. 4) Afferent units which responded to distension of the colon and to bradykinin were also excited by partial or complete ischaemia of the colon (produced by occlusion of both mesenteric arteries or of only the inferior mesenteric artery). During ischaemia the activity in the afferents increased and became burst-like. The response to distension of the colon increased in some of the afferent units. 5) Blood pressure responses to colon distension and to local bradykinin application also increased during ischaemia. 6) The results indicate that visceral afferent fibres from the colon in the inferior splanchnic nerves may be functionally homogeneous and may encode noxious stimuli applied to the colon.     

Myelinated afferent fibres innervating the primate skin and their response to noxious stimuli

1. The functional characteristics of cutaneous receptors in the squirrel monkey were determined by recording discharges of single myelinated afferent fibres in peripheral nerves with micro-electrodes or from fine filaments prepared by dissection. One hundred and sixty-nine fibres of the posterior femoral cutaneous nerve and 209 of the superficial radial nerve with conduction velocities between 4 and 88 m/sec were classified according to the nature of the most effective stimulus, discharge characteristics, adaptation rate and organization of the receptive field.2. Twenty per cent of the fibres innervating either hairy or glabrous skin required strong mechanical stimuli for activation; thresholds ranged from moderate to overtly damaging pressures. This class showed little or no sensitivity to thermal changes including noxious heat. Their receptive fields consisted of numerous, mechanically-excitable points or spots. All such fibres gave higher impulse frequencies to noxious than to innocuous mechanical stimuli and a large fraction were considered to be nociceptors because they responded only to noxious deformation. The conduction velocities of nociceptors were distributed between 5 and 28 m/sec.3. All but a few of the other fibres encountered responded vigorously to innocuous stimuli and were readily identified as corresponding to one of the receptor types known to exist in either the primate or the cat. These sensitive receptors were systematically tested by intense cutaneous stimuli; their response to injurious stimuli always could be mimicked by innocuous ones.4. Therefore, in the primate a particular class of slowly-conducting myelinated fibres is partially responsible for signalling mechanically-induced cutaneous damage. The probable relation between such afferent fibres and certain kinds of cutaneous pain is explored.     

Myelinated afferent fibres responding specifically to noxious stimulation of the skin

1. The characteristics of receptors from the hairy skin of the hind limb of cat were studied by recording from single primary afferent fibres with fine micropipettes. The distinctive features of 513 fibres conducting under 51 m/sec are described.2. Seventy-four fibres conducting between 6 and 37 m/sec were classified as nociceptors because they responded only to damaging mechanical stimulation of the skin. These fibres responded maximally to pinching the skin with a serrated forceps or to cutting the skin. Noxious heat, noxious cold, acid applied to the receptive field and bradykinin injected into skin cuts did not evoke discharges from such receptors. Typically their receptive fields were 2-5 cm long by 1-2·5 cm wide and consisted of responsive spots (under 1 mm diameter) separated by unresponsive areas. There was a tendency for the most slowly conducting fibres so classified to be the least sensitive.3. Other afferent fibres had receptive fields similar to the nociceptors; however, they were excited by substantial but not noxious mechanical deformation. Their conduction velocities overlapped those of the nociceptors and extended upwards to 51 m/sec; the most rapidly conducting fibres tended to be the most sensitive to mechanical stimuli. These insensitive mechanoreceptors or moderate pressure receptors adapted more slowly than the nociceptors.4. The majority of fine myelinated axons originated from hair receptors and had conduction velocities concentrated between 14 and 22 m/sec.5. The possible relation of these observations to pain and reactions typical of pain is considered.     

Encoding of nociceptive thermal stimuli by diffuse noxious inhibitory controls in humans

1. It has previously been shown that, in normal humans, heterotopic painful thermal conditioning stimuli induce parallel increase in the thresholds of a spinal nociceptive flexion reflex (RIII reflex) and the concurrent sensation of pain elicited by electrical stimulation of the sural nerve. On the basis of analogous animal studies, we proposed that such phenomena could be related to diffuse noxious inhibitory controls (DNIC), which have been described in the rat. The present study, which was carried out on normal volunteer subjects, was particularly concerned with the extent and temporal characteristics of the depressive effects of DNIC triggered by painful thermal stimuli on RIII reflex activity. In addition, because it was possible that these depressive effects could have resulted from a direct postsynaptic inhibition of motoneurons, a second part of the study was aimed at determining whether or not the heterotopic noxious thermal stimuli also affected the excitability of alpha-motoneurons, as monitored by the monosynaptic Hoffmann reflex (H reflex) technique. 2. In the 11 subjects under study, application of moderate, nonnoxious temperatures (40-44 degree C) to the contralateral hand (via a thermoregulated and agitated waterbath) did not modify the RIII reflex nor the associated sensation of pain. By contrast noxious temperatures clearly depressed the RIII reflex and the concurrent sensation of pain, both during and after the conditioning procedure (CP), in a direct linear relationship to the temperature of the waterbath in the 45-47 degree C range; the maximal depressive effect was observed with the highest conditioning temperature. A significant relationship was also found between the extent of the RIII depression during the CP and that during a 10-min period of post-CP observation. 3. The depressive effects observed on both the RIII reflex and pain were not associated with clear change in autonomic functions. Respiration remained stable during the sessions, with no significant relationship between the temperatures of the waterbath and respiratory rate. Heart rate was slightly but significantly increased during the immersion of the hand in the 46 or 47 degree C waterbaths; this increase, however, ceased with the end of CP. 4. Application of thermal conditioning stimuli produced a slight but nonsignificant increase of the monosynaptic H reflex during the first minute of CP, no matter what was the temperature of the waterbath. However, there were no subsequent variations during the 6-min period of post-CP observation.(ABSTRACT TRUNCATED AT 400 WORDS)     

PAD patterns of physiologically identified afferent fibres from the medial gastrocnemius muscle

Summary Intracellular recordings were made in the barbiturate-anesthetized cat from single afferent fibres left in continuity with the medial gastrocnemius muscle to document the transmembrane potential changes produced in functionally identified fibres by stimulation of sensory nerves and of the contralateral red nucleus (RN). Fifty five fibres from muscle spindles had conduction velocities above 70 m/s and were considered as from group Ia. Stimulation of group I afferent fibres of the posterior biceps and semitendinosus nerve (PBSt) produced primary afferent depolarization (PAD) in 30 (54%) Ia fibres. Stimulation of the sural (SU) nerve produced no transmembrane potential changes in 39 (71%) group Ia fibres and dorsal root reflex-like activity (DRRs) in 16 (29%) fibres. In 17 out of 28 group Ia fibres (60.7%) SU conditioning inhibited the PAD generated by stimulation of the PBSt nerve. Facilitation of the PBSt-induced PAD by SU conditioning was not seen. Repetitive stimulation of the RN had mixed effects: it produced PAD in 1 out of 8 fibres and inhibited the PAD induced by PBSt stimulation in 2 other fibres. Nine fibres connected to muscle spindles had conduction velocities below 70 m/s and were considered to be group II afferents. No PAD was produced in these fibres by SU stimulation but DRRs were generated in 5 of them. In 23 out of 31 fibres identified as from tendon organs group I PBSt volleys produced PAD. However, stimulation of the SU nerve produced PAD only in 3 out of 34 fibres, no transmembrane potential changes in 30 fibres and DRRs in 1 fibre. The effects of SU conditioning on the PAD produced by PBSt stimulation were tested in 19 Ib fibres and were inhibitory in 12 of them. In 9 of these fibres SU alone produced no transmembrane potential changes. Repetitive stimulation of the RN produced PAD in 3 out of 9 Ib fibres. SU conditioning inhibited the RN-induced PAD. The present findings support the existence of an alternative inhibitory pathway from cutaneous to Ib fibres, in addition to the well known excitatory pathway producing PAD. Possible functional implications of inhibitory actions of cutaneous fibres with the pathways mediating the PAD of group Ia and Ib fibres are discussed.     

Functional characteristics of lumbar visceral afferent fibres from the urinary bladder and the urethra in the cat

Neural activity of lumbar visceral afferents supplying the urinary bladder and urethra was analyzed systematically in the cat. The afferent fibres were isolated either from the white rami L3 and L4 in a preparation with closed peritoneal cavity, or from the lumbar splanchnic nerves in a preparation with open peritoneal cavity and investigated for various functional parameters. Seventy five single units and 9 multiunit bundles were analyzed. 1) About 50% of the afferent units had some ongoing activity (0.2 to 1 imp/s). Two thirds of the afferent axons were thin myelinated (conduction velocity 3–15 m/s), the rest were presumably unmyelinated (conduction velocity below 2 m/s). 2) The receptive fields of the afferent units consisted —with one exception — of single mechanosensitive sites on the surface of the bladder and urethra. Most receptive fields were situated on the dorsal side of the bladder. 3) Afferents with receptive fields on or in the bladder wall responded in a graded manner to passive distension and isovolumetric contraction at intravesical pressures ranging from about 10 to 70 mm Hg. The thresholds for exciting the afferent units ranged from less than 10 mm Hg to about 30 mm Hg intravesical pressure, most of them being less than 20 mm Hg. Generally, the discharge rate of the afferent units gave a reliable representation of the intravesical pressure to the lumbar spinal cord. 4) Urethral units exhibited either no responses to the graded distensions and contractions of the urinary bladder, or responded with low discharge rates at higher intravesical pressures. 5) The results do not support the notion that noxious events in the urinary bladder are encoded by specific nociceptive visceral afferents to the lumbar spinal cord but possibly by some other mechanism of encoding.Supported by the Deutsche Forschungsgemeinschaft     

内脏伤害性刺激在脊髓突触后背柱神经元的信号转导机制

内脏痛是急慢性胃肠道、盆腔、泌尿道和其它实体器官疾病的最常见症状之一。许多疾病伴发的内脏性疼痛十分顽固,如肠道激惹综合征、间质性膀胱炎、胰腺炎、子宫内膜异位症和癌性内脏痛等,给临床医师带来了极大的挑战。内脏疼痛机制十分复杂。近年来,一系列的临床和基础研究发现起源于     

Discharge patterns of afferent cutaneous nerve fibers from the rat's tail during prolonged noxious mechanical stimulation

Summary Feedback controlled constant force stimuli of 4, 6 and 8 N intensities and of 120 s duration were applied to the receptive fields of cutaneous afferent fibers in the rat's tail. Two types of nociceptive units showed sustained discharges during these stimuli: polymodal unmyelinated C-units (MH-C units, N = 18, c.v. 0.5–0.9 m/s) and high-threshold mechanoreceptive A-delta-units(HTM-units, N=10, c.v. 1.9–11.2 m/s). In addition two classes of sensitive low threshold mechanoreceptors, SA I (N=6) and SA II (N=5) units, responded to the prolonged mechanical stimuli. At the onset of a noxious pressure, 11 of the 18 polymodal nociceptors exhibited dynamic responses (lasting about 10 s) which were followed by slowly adapting tonic discharges that lasted for the duration of the stimuli. The remaining polymodal C-fiber units (8/18) did not show dynamic discharges at 4 and 6 N. Phasic and tonic discharges were positively correlated with stimulus strength. The HTM-units encoded stimulation intensity mainly by their dynamic discharges. The tonic discharges of these units displayed faster adaptation rates with stronger mechanical stimuli, i.e. encoding of stimulation intensity became progressively weaker during the tonic phase. The discharges of sensitive SA I and SA II units with A beta axons were not positively correlated with the strength of noxious pressure stimuli. Tonic discharge rates of SA I units were negatively correlated to stimulus strength, whereas SA II units usually stopped firing in the course of a stimulus and became reversibly irresponsive to mechanical stimulation. Possible afferent mechanisms underlying the induction of pain by sustained noxious mechanical stimulation are discussed.     

The response of laryngeal afferent fibres to mechanical and chemical stimuli

1. We have recorded afferent activity from ;single fibres' dissected from the superior laryngeal nerve of anaesthetized cats.2. Units which responded to gentle mechanical stimulation of the larynx epithelium were chosen for study.3. Receptors with myelinated fibres were grouped according to their spontaneous activity. Group 1 fibres had little or no spontaneous activity: group 2 fibres had constant and continuous spontaneous activity.4. Group 1 fibres had a wide range of adaptation rates. Their conduction velocities lay between 3.0 and 30 m/sec. The receptors were generally stimulated by ammonia and distilled water and often by CS riot control agent, 5 and 10% CO(2), 200 ppm SO(2), and cigarette smoke. Histamine, phenyl diguanide, graphite dust, 100 ppm SO(2) and saline drops did not generally excite the fibres.5. Group 2 fibres were slowly adapting. Their conduction velocities ranged between 8.0 and 26.5 m/sec. Ammonia usually, and distilled water sometimes, excited these fibres while 5 and 10% CO(2) mixtures inhibited them. A minority of group 2 fibres were pH sensitive, inhibited by acids and stimulated by alkaline buffers. Cigarette smoke had complex actions, either excitation, inhibition or, at different times, both. Histamine, P.d.g., CS, SO(2), saline drops and dust had no action on these fibres.6. Recordings were made from one unmyelinated fibre (conduction velocity 1.9 m/sec) which responded to stroking of the epithelium with a thread and to histamine, P.d.g. and ammonia vapour applied to the epithelium.7. We consider the site, method of excitation and reflex actions of the different receptors described.     

Capsaicin desensitization of peripheral nociceptive fibres does not impair sensitivity to other noxious stimuli

Capsaicin was tested on peripheral fibres in vitro to determine whether evoked depolarization or desensitization were likely to explain the antinociception observed after acute systemic capsaicin in vivo. The activation of peripheral fibres by noxious (capsaicin, bradykinin, heat) and innocuous (light brush) stimuli was recorded as a depolarization of a spinal ventral root (L3-L5) in the neonatal rat spinal cord with attached tail. Prolonged superfusion of the tail with low doses (0.2-2 microM) of capsaicin produced a short lasting depolarization followed by a complete loss of sensitivity to capsaicin without changes in sensitivity to other noxious or innocuous stimuli. Partial recovery from this selective desensitization could be observed 3-5 h later. In most preparations superfusion of the tail with 20 microM capsaicin produced a prolonged and non-selective impairment of sensitivity to all noxious stimuli. These data suggest that neither depolarization by capsaicin nor the selective desensitization of peripheral fibres to capsaicin are likely to account for the acute antinociceptive effect of systemic capsaicin. On the other hand the non-selective reduction in sensitivity to noxious stimuli induced by capsaicin may contribute to its antinociceptive action.     

Reflex discharge patterns of cardiac vagal efferent fibres

1. Unit activity was recorded from single and few fibre preparations in a cardiac branch of the right vagus nerve of the cat.2. Increases in blood pressure mediated solely by the right carotid sinus nerve produced bradycardia when all other nerves to the heart had been cut. Myelinated fibres in the cardiac branch of the right vagus nerve were reflexly activated by the same procedure.3. The fibres were silent when blood pressure was below 140-150 mm Hg. As the pressure began to rise, they discharged phasically with the cardiac cycle. At pressures greater than 180 mm Hg, the discharge was continuous attaining maximum rates of 40/sec.4. Stimulation of carotid body chemoreceptors also reflexly excited these fibres, as did stimulation of baroreceptors in both the left carotid sinus and aortic arch. Afferent fibres in the left vagus discharging in response to changes in blood pressure reflexly excited the cardiac efferent fibres. Increases in phrenic motoneurone discharge coincided with inhibition of these fibres. Electrical stimulation of the glossopharyngeal nerve also produced inhibition.     

Characterization of neuronal responses to noxious visceral and somatic stimuli in the medial lumbosacral spinal cord of the rat

The cutaneous receptive fields, long ascending projections, and responses to colorectal distension (20-100 mmHg) and tail movement of 252 neurons in spinal segments L6-S1 were characterized in pentobarbital- or halothane-N2O anesthetized, physiologically intact male rats. Seventeen additional neurons were studied in spinalized rats. Neurons studied were located within 0.5 mm of the midline at depths 0.2-1.4 mm from the spinal cord dorsum and included the area immediately dorsal and lateral to the central canal. Colorectal distension and/or antidromic invasion from the contralateral ventral quadrant of the cervical spinal cord were used as search stimuli. One hundred seventeen neurons responded to noxious colorectal distension; many had long ascending projections and convergent somatic input from deep joint receptors, ipsilateral perianal/scrotal cutaneous receptive fields, or both. Stimulus-response functions (SRFs) of 45 neurons to graded colorectal distension were linear, allowing extrapolation of threshold distending pressures to neuronal response. Neurons responsive to colorectal distension were subdivided into four classes based on their initial response colorectal distension (75-80 mmHg, 20 s). Short-latency abrupt (SL-A) neurons were excited at short latency by colorectal distension; activity abruptly returned to base line following termination of distension. Most SL-A neurons had long ascending projections, convergent somatic receptive fields, and 4/6 tested were excited by bradykinin administered intraarterially. The threshold distending pressure, estimated from the SRFs of 19 SL-A neurons, extrapolated to 2.7 mmHg. Short-latency sustained (SL-S) neurons were also excited at short latency by colorectal distension, but responses were sustained for 4-120 s following termination of distension. Most SL-S neurons had long ascending projections, convergent somatic receptive fields, and 18/20 tested were excited by intraarterial bradykinin. The threshold distending pressure, estimated from the SRFs of 20 SL-A neurons, extrapolated to 17.0 mmHg. Long-latency (LL) neurons were excited by colorectal distension at long latency following the onset of distension. No LL neurons had demonstrable long ascending projections, and few had convergent excitatory somatic fields. Three of five LL neurons were excited by intraarterial bradykinin. The threshold distending pressure, estimated from the SRFs of six LL neurons, extrapolated to 9.8 mmHg. Inhibited (INHIB) neurons were spontaneously active and were inhibited by colorectal distension.(ABSTRACT TRUNCATED AT 400 WORDS)     

Encoding of electrical, thermal, and mechanical noxious stimuli by subnucleus reticularis dorsalis neurons in the rat medulla

1. In anesthetized rats, recordings were made within the medullary subnucleus reticularis dorsalis (SRD) from neurons that exhibited convergence of nociceptive inputs from the entire body. Neurons with total nociceptive convergence (TNC) responded to suprathreshold percutaneous electrical stimuli (2-ms duration) with an early and a late peak due to activation of A delta- and C-fibers, respectively, no matter which part of the body was stimulated. Neurons with partial nociceptive convergence (PNC) responded to the same stimuli with an A delta-peak regardless of which part of the body was stimulated and with a C-peak of activation from some, mainly contralateral, parts of the body. The characteristics of the responses of these neurons to the application of graded intensities of electrical, thermal, and mechanical stimuli were analyzed. 2. All TNC neurons and 85% of PNC neurons responded to A delta- and C-fiber activation following percutaneous electrical stimulation of the contralateral hindpaw. With regard to A delta-fiber-evoked responses, a linear relationship between the logarithm of the applied current and the magnitude of the responses was found within the 0.25- to 6.0-mA and 0.5- to 24-mA ranges for TNC and PNC neurons, respectively; however, these curves were essentially similar. With regard to C-fiber-evoked responses, such a linear relationship was found within the 1.5- to 6.0-mA range for both types of SRD neurons, although the TNC neurons presented larger C-fiber-evoked responses than did the PNC neurons. 3. TNC and PNC neurons linearly increased their discharges during the application of noxious thermal stimuli to the contralateral hindpaw within the range 44-52 degrees C; the mean responses evoked by noxious heat from TNC neurons were of higher magnitude than those from PNC neurons. The majority of SRD neurons presented long-lasting afterdischarges, especially with the highest temperature employed (52 degrees C). 4. TNC neurons monotonically increased their discharges during graded mechanical or thermal stimulation of the tail. When mechanical stimuli were applied, a linear relationship was found between the logarithm of the strength of the mechanical stimulus and the neuronal discharges, in the 5.3- to 7.4-N/cm2 range. With thermal stimulation, TNC neurons linearly increased their discharges in the 44-52 degrees C range. When increasing amounts of the tail were immersed in a 50 degrees C waterbath, TNC neurons increased their discharges within a restricted range of tail surface areas (0.9-5.7 cm2); further increases in the stimulated surface size were not followed by increases in firing rate.(ABSTRACT TRUNCATED AT 400 WORDS)     

Termination patterns of identified group II and III afferent fibres from deep tissues in the spinal cord of the cat

In chloralose-anaesthetized cats, the impulse activity of single afferent fibres supplying receptors in the deep tissues of the hindlimb (fasciae, muscles, ligaments, joint capsules) was recorded using micropipettes filled with a solution of horseradish peroxidase. Only myelinated fibres with conduction velocities up to 40 m/s (Group III and Group II units) were studied, i.e. fast conducting afferent fibres from muscle spindles and tendon organs were excluded. The fibres were functionally characterized with the use of mechanical stimuli such as local pressure and joint movements. The results show that a relationship exists between the functional properties of a given afferent unit and the location of its terminals in the spinal cord. Since the conduction velocity and hence the diameter of the fibres was similar in all the units studied, these factors appear not to be of importance for determining the pattern of spinal termination. Out of 84 units, 42 were classified as high-threshold mechanosensitive, 26 as low-threshold mechanosensitive, and 16 as secondary endings from muscle spindles. Following physiological identification the fibres were ionophoretically injected with horseradish peroxidase and their trajectory in the white and gray matter of the spinal cord visualized histologically with diaminobenzidine. High-threshold mechanosensitive units took a lateral course in the posterior funiculus and usually did not bifurcate. They exhibited two different patterns of spinal termination, one being characterized by terminal arborizations in both lamina I and deeper laminae (mostly IV/V), the other one by an exclusive projection to lamina I. Low-threshold mechanosensitive units often showed a bifurcation in the posterior funiculus and did not have a uniform termination pattern. The main areas of termination were lamina II and laminae IV-VI. The slowly conducting secondary endings from muscle spindles projected mainly to laminae VI and VII with additional collaterals entering the ventral horn. They thus had a termination pattern similar to that reported for fast conducting afferent fibres (above 50 m/s) from muscle spindle secondary endings. With the exception of one high-threshold mechanosensitive unit none of the stained fibres possessed terminal arborization and boutons in lamina III. It is concluded that different types of Group II and III primary afferent fibres from deep tissues exhibit different patterns of spinal termination.(ABSTRACT TRUNCATED AT 400 WORDS)