Higher Mechanical Thresholds Research Articles

Chemosensitivity of nociceptive, mechanosensitive afferent nerve fibres in the guinea-pig ureter.

The mechanosensitivity and chemosensitivity of afferent fibres were investigated in an in vitro preparation of the guinea-pig ureter. Electrophysiological recordings were obtained from 5 U-1 (low mechanical threshold, contraction-sensitive) and 74 U-2 units (high threshold). U-2 units had significant higher levels of spontaneous activity, lower conduction velocities, higher mechanical thresholds (U-1: 7 mmHg; U-2: 39 mmHg), less pronounced phasic responses and longer latencies in the response to distensions than the U-1 units. For chemical stimulation, guinea-pig urine (> 800 mosmol/L), bradykinin and capsaicin were applied intraluminally. The responses of U-1 units mainly corresponded to the contractions induced by the chemical stimulation. The vast majority of the U-2 units were excited by urine, bradykinin (threshold: 0.1-1 microM) and capsaicin (threshold: 0.03-0.3 microM). The responses to urine could be mimicked by high concentrations of potassium ions (> 200 mM), but not by an equiosmolar solution of NaCl, urea and mannitol. Chemical stimulation could also result in a transient sensitization of the U-2 units to mechanical stimuli. In the anaesthetized guinea-pig, pseudo-affective responses could be evoked by ureteric distension (threshold: 30-60 mmHg) and serosal application of capsaicin. Intraluminal application of urine in vivo did not evoke any reactions, suggesting that the responses of the U-2 units to urine might be due to an impaired barrier function of the urothelium in vitro. The data are in agreement with the hypothesis that U-2 units are visceral polymodal nociceptors. Since the U-1 units were also able to encode at least noxious mechanical stimuli, their involvement in visceral nociception cannot be excluded.

Receptive properties of mouse sensory neurons innervating hairy skin.

Using an in vitro nerve skin preparation and controlled mechanical or thermal stimuli, we analyzed the receptive properties of 277 mechanosensitive single primary afferents with myelinated (n = 251) or unmyelinated (n = 26) axons innervating the hairy skin in adult or 2-wk-old mice. Afferents were recorded from small filaments of either sural or saphenous nerves in an outbred mice strain or in the inbred Balb/c strain. On the basis of their receptive properties and conduction velocity, several receptor types could be distinguished. In adult animals (>6 wk old), 54% of the large myelinated fibers (Abeta, n = 83) showed rapidly adapting (RA) discharges to constant force stimuli and probably innervated hair follicles, whereas 46% displayed a slowly adapting (SA) response and probably innervated Merkel cells in touch domes. Among thin myelinated fibers (Adelta, n = 91), 34% were sensitive D hair receptors and 66% were high-threshold mechanoreceptors (AM fibers). Unmyelinated fibers had high mechanical thresholds and nociceptive functions. All receptor types had characteristic stimulus-response functions to suprathreshold force stimuli. Noxious heat stimuli (15-s ramp from 32 to 47 degrees C measured at the corium side of the skin) excited 26% (5 of 19) of AM fibers with a threshold of 42.5 +/- 1.4 degrees C (mean +/- SE) and an average discharge of 15.8 +/- 9.7 action potentials and 41% (7 of 17) C fibers with a mean threshold of 37.6 +/- 1.9 degrees C and an average discharge of 22.0 +/- 6.0 action potentials. Noxious cold stimuli activated 1 of 10 AM fibers and 3 of 10 C fibers. One of 10 C units responded to both heat and cold stimuli. All types of afferent fibers present in adult mice could readily be recognized in mice at postnatal day 14. However, fibers had reduced conduction velocities and the stimulus-response function to mechanical stimuli was more shallow in all fibers except for the D hairs. In juvenile mice, 22% of RA units also displayed an SA response at high stimulus intensities; these units were termed RA/SA units. We conclude that all types of cutaneous afferent fibers are already committed to their phenotype 2 wk after birth but undergo some maturation over the following weeks. This preparation has great potential for the study of transgenic mice with targeted mutations of genes that code factors that are involved in the specification of sensory neuron phenotypes.

The effect of topical turpentine on the functional properties of cutaneous afferents in the anaesthetized rat

Turpentine was applied to the rat dorsal hindpaw over 1.5–3.5 h and afferent activity was recorded for 1.5–7 h after its removal. Increased spontaneous activity from both A- and C-fibres was observed. There was an increase in units with no response to natural stimuli and a reduction in the numbers of all types of afferent unit, with some recovery of the C- and A δ-classes during the recording period. Surviving C-polymodal nociceptor units had normal sensitivity to noxious heat, but higher mechanical thresholds. Thus turpentine application caused no nociceptor sensitization. Instead, the many insensitive units plus the generalized spontaneous firing may be signs of non-specific axonal damage. A general division of irritant chemicals into those that are predominately damaging, like turpentine, and those that generate specific nociceptor firing or sensitization, is proposed.

Neurons in the chicken ureter are innervated by substance P- and calcitonin gene-related peptide-containing nerve fibres: immunohistochemical and electrophysiological evidence.

Numerous ganglia or single neurones immunoreactive to protein gene-product 9.5 (PGP) were demonstrated in the chicken ureter. Ganglia were observed in the main nerve trunks accompanying the ureter (400-2,000 cells), in the adventitia (1-45 cells; density; 79 +/- 12 ganglia/cm2; mean +/- S.E.M.), in the circular muscle (1-9 cells; 76 +/- 10 ganglia/cm2) and in the longitudinal muscle (1-8 cells; 232 +/- 41 ganglia/cm2). Most of the PGP-positive neurones in the nerve trunk ganglia (approximately 66%) and in the smooth muscle layers (85%) were encircled by a dense plexus of varicose nerve fibres containing both substance P (SP) and calcitonin gene-related peptide (CGRP). SP-positive somata were rarely observed. Immunogold electron microscopy revealed that SP- and CGRP-immunoreactivity were colocalised in the same dense core vesicles. A strong reduction of SP-positive nerve fibres was observed in organ cultures of the ureter, indicating their extrinsic origin. The fibres might originate from the dorsal root ganglia, where SP and CGRP were colocalised in 20-30% of the neurones. The sensitivity of ureteric neurones to SP and CGRP was investigated in recordings obtained from mechanosensitive nerve fibres with cell bodies located in or adjacent to the ureter (U-G units). The majority (71%) of the U-G units was excited by local application of SP in a dose-dependent manner. The SP-sensitive U-G neurones had higher mechanical thresholds (29 +/- 5 mmHg) as opposed to the SP-insensitive ones (10 +/- 3 mmHg). Repeated applications of high doses of SP to the U-G units resulted in desensitisation and reduced the response to mechanical stimuli. None of the U-G units responded to local application of CGRP, but all U-G units were excited by acetylcholine. The data support the hypothesis that SP-containing primary afferents are involved in the modulation of the activity of ureteric neurons in the chicken.

The characteristics of slowly adapting mechanical sensory neurons in the trigeminal ganglia of crotaline snakes

Mechanical pressure (P) and touch (M) neurons, two types of slowly adapting neurons, can be distinguished in the trigeminal ganglion of crotaline snakes, Trimeresurus flavoviridis, by their electrophysiological membrane properties. Intracellular stimulation and the recording of the responses from P and M neurons in vivo was performed with microelectrodes. The characteristics of the receptive field (RF) of both types of neurons were examined. P neurons had a much larger RF size and a higher mechanical threshold than those of M neurons. Both of them responded with discharges to mechanical stimulation. The active and passive electrophysiological membrane properties were measured from nine P and 18 M neurons. The active membrane properties of P neurons showed a larger amplitude and longer duration of action potential, a larger after-hyperpolarization with a longer duration to half-decay, and a higher electric threshold in response to intracellularly injected depolarizing current than M neurons. The passive membrane properties of P neurons showed a higher input resistance, much longer time constant, and larger capacitance than M neurons. The rebound spike which responded to injecting sufficient hyperpolarizing current was sometimes observed, and had a longer latency in P neurons than M neurons. These results indicated that some electrophysiological membrane properties of primary sensory neurons are dependent on their sensory modalities.

Pain from excitation of identified muscle nociceptors in humans

The technique of intraneural microstimulation (INMS) combined with microneurography was used to excite and to record impulse activity in identified afferent peroneal nerve fibers from skeletal muscle of human volunteers. Microelectrode position was minutely adjusted within the impaled nerve fascicle until a reproducible sensation of deep pain projected to the limb was obtained during INMS. During INMS trains of 5–10 s in duration and at threshold for sensation, volunteers perceived a well defined area of deep pain projected to muscle. Psychophysical judgements of the magnitude of pain increased with increasing rates of INMS between 5 and 25 Hz. Also, the area of the painful projected field (PF) evoked during trains of INMS of various duration but constant intensity and rate typically expanded with duration of INMS. The intraneural microelectrode was alternatively used to record neural activity originating from primary muscle afferents. Eight slowly adapting units with moderate to high mechanical threshold were identified by applying pressure within or adjacent to the painful PF. Conduction velocities ranged from 0.9 to 6.0 m/s, and fibers were classed as Group III or Group IV. Capsaicin (0.01%) injected into the RF of two slowly conducting muscle afferents (one Group III and one Group IV) produced spontaneous discharge of each fiber and caused intense cramping pain, suggesting that the units recorded were nociceptive. Our results endorse the concept that the primary sensory apparatus that encodes the sensation of cramping muscle pain in humans is served by mechanical nociceptors with slowly conducting nerve fibers. Results also reveal that muscle pain can be precisely localized, although the human cortical function of locognosia for muscle pain becomes blunted as a function of duration of the stimulus.

Interganglionic segregation of distinct vagal afferent fibre phenotypes in guinea-pig airways.

1. The present study addressed the hypothesis that jugular and nodose vagal ganglia contain the somata of functionally and anatomically distinct airway afferent fibres. 2. Anatomical investigations were performed by injecting guinea-pig airways with the neuronal tracer Fast Blue. The animals were killed 7 days later, and the ganglia were removed and immunostained with antisera against substance P (SP) and neurofilament protein (NF). In the nodose ganglion, NF-immunoreactive neurones accounted for about 98% of the Fast Blue-labelled cells while in the jugular ganglion they accounted for approximately 48%. SP and NF immunoreactivity was never (n = 100) observed in the same cell suggesting that the antisera labelled distinct populations. 3. Electrophysiological investigations were performed using an in vitro guinea-pig tracheal and bronchial preparation with intact afferent vagal pathways, including nodose and jugular ganglia. Action potentials arriving from single airway afferent nerve endings were monitored extracellularly using a glass microelectrode positioned near neuronal cell bodies in either ganglion. 4. The nodose ganglion contained the somata of mainly fast-conducting tracheal A delta fibres whereas the jugular ganglion contained equal numbers of C fibre and A delta fibre tracheal afferent somata. The nodose A delta neurones adapted rapidly to mechanical stimulation, had relatively low mechanical thresholds, were not activated by capsaicin and adapted rapidly to a hyperosmotic stimulus. By contrast, jugular A delta and C fibres adapted slowly to mechanical stimulation, were often activated by capsaicin, had higher mechanical thresholds and displayed a slow adaptation to a hyperosmotic stimulus. 5. The anatomical, physiological and pharmacological data provide evidence to support the contention that the vagal ganglionic source of the fibre supplying the airways ultimately dictates its neurochemical and physiological phenotype.

Mechanical response properties of nociceptors innervating feline hairy skin.

1. The responses of feline cutaneous nociceptors were examined in vivo by systematically manipulating the intensive and spatial dimensions of mechanical stimulation. A computer-controlled motor was used to apply prescribed forces (5-90 g) to a nociceptor's receptive field, with flat-tipped, cylindrical probes of various sizes (contact areas: 0.1-5.0 mm2). The stimulating device and protocols were similar to those previously used to evaluate human perception, thus allowing for comparisons of the two data sets. 2. With a ramp-and-hold stimulus of controlled force, most nociceptors showed a slowly adapting (SA) response throughout the stimulus. In this way, nociceptors resembled low-threshold SA mechanoreceptors. However, in contrast to SA mechanoreceptors, nociceptors failed to exhibit an onset burst of activity associated with the stimulus ramp. Nineteen percent (6 of 31) of the nociceptors often showed the opposite trend during the stimulus, e.g., a gradually increasing firing rate. Most of these nociceptors (5 of 6) had particularly high mechanical thresholds. 3. With 30 stimuli repeated at short intervals (6-8 s), response rates tended to decrease across trials. This phenomenon was most evident with more intense stimuli. When two series of stimuli were separated by 4-5 min, there was no apparent trend of reduced responsiveness between series. 4. Overall, nociceptors responded in an orderly way to variations in force and probe size. For a given probe size, larger forces produced greater responses; for a given force, smaller probes produced greater responses. The relationship between probe size and force was best described as an even tradeoff between force and a linear dimension of the probe (i.e., probe perimeter), rather than the area of the probe. Thus a given pressure (force/area) did not evoke the same response from nociceptors as probe size was varied. 5. There were two significant differences in the mechanical responsiveness between A fiber and C fiber nociceptors. First, for a given set of stimuli, A fiber nociceptors exhibited a greater response rate than the C fiber nociceptors. Second, the A fiber nociceptors exhibited a greater differential response related to probe size than the C fiber nociceptors. On the basis of these two features, the A fiber nociceptors' response profiles showed a closer parallel with previously reported human pain thresholds than the C fiber nociceptors did. 6. When the nociceptors were subdivided as to their mechanical threshold, those with lower thresholds [mechanically sensitive afferents (MSAs)] showed a response saturation with the more intense stimuli. On average, the stimulus levels at which saturation occurred were close to human pain threshold. Those nociceptors with higher thresholds [mechanically insensitive afferents (MIAs)] did not show such saturation. Thus only the MIAs appeared to have the capacity to unambiguously encode mechanical stimulus intensities above pain threshold. The MSAs, on the other hand, exhibited their greatest dynamic response range near the threshold for nonpainful sharpness. Thus the group of afferents commonly defined as nociceptors exhibit a heterogeneity of mechanical response properties, which may serve functionally different roles for perception.

Mitochondria in fine afferent nerve fibres of the knee joint in the cat: a quantitative electron-microscopical examination.

The distribution of mitochondria, their content and concentration (expressed as the ratio of the mean volume of mitochondria and the surface of the sensory axon) were determined in group-III and -IV nerve fibres innervating the knee joint capsule in the cat. Mitochondria mainly accumulated in axonal swellings ("beads") and end bulbs of the terminal branches. Between single nerve fibres, marked differences in the content and the concentration of mitochondria were obtained in proximal portions (inside of the perineurium) and in distal portions (unmyelinated sensory endings). In group-III nerve fibres, the mitochondrial concentration ranged from 0.005 to 0.030 microns 3/microns 2 (proximal portion) and from 0.016 to 0.080 microns 3/microns 2 (distal portion). In unmyelinated group-IV nerve fibres, the values also showed a broad variation ranging from 0.001 to 0.011 microns 3/microns 2 (proximal portion) and from 0.003 to 0.019 microns 3/microns 2 (distal portion). The wide range of mitochondrial concentrations may reflect different energy consumption during receptive processes: nerve fibres with a low mechanical threshold and a high probability of excitatory events may be rich in mitochondria, whereas fibres with a high mechanical threshold and a low probability of excitatory events may be poor in mitochondria.

Mechanosensitive Afferent Units in the Lumbar Intervertebral Disc and Adjacent Muscle

The purpose of this study was to characterize the somatosensory units of the lumbar intervertebral disc and adjacent muscle. A laminectomy was performed on the lumbar spine of adult male Japanese White rabbits. Receptive fields of mechanosensitive afferent units were investigated in the intervertebral disc and adjacent muscle, and electrophysiologic recordings were obtained from filaments of the dorsal root. Thirteen mechanosensitive units were identified: three units in the intervertebral disc area, and 10 units in the psoas muscle. Of the three units in the disc area, one was identified at the surface of the L5-6 anulus fibrosus and two at the insertion of the anulus fibrosus to the L5 and L6 vertebral bodies. These three units belonged to Group III and had very high mechanical thresholds, more than 160 g. The 10 units in the psoas muscle belonged to Groups II, III, and IV, and had mechanical thresholds ranging from 0.22 to 12.6 g. The units in the disc area may serve as nociceptors sensitive to strong noxious stimulation that could traumatize the tissue. The units in the psoas muscle may contribute to nociception and proprioception.

Appearance of new receptive fields in rat dorsal horn neurons following noxious stimulation of skeletal muscle: a model for referral of muscle pain?

To test the hypothesis that painful stimuli to skeletal muscle lead to a widespread unmasking of synaptic connections in dorsal horn neurons, intramuscular injections of bradykinin (BKN) were made outside the receptive fields (RFs) of these cells in the rat. Following BKN injections, new RFs all of which were located in the deep tissues and had high mechanical thresholds appeared in 9 out of 21 (42.8%) nociceptive dorsal horn neurons which originally had a single RF in deep tissues or in the skin. The apperance of new RFs may lead to a mislocation of the source of pain if in fact the impulse activity of a nociceptive dorsal horn neuron contains information on the site of the stimulus.

Chemosensitivity and sensitization of nociceptive afferents that innervate the hairy skin of monkey.

1. A large proportion of the cutaneous nociceptor population in monkey either does not respond to mechanical stimuli or has very high mechanical thresholds (> 6 bar). The goal of this study was to determine whether these mechanically insensitive nociceptive afferents (MIAs) differ from mechanically sensitive nociceptive afferents (MSAs) with regard to responses to chemical stimuli. 2. Teased-fiber techniques were used to record from 28 A delta-fiber (16 MIAs and 12 MSAs) and 23 C-fiber (10 MIAs and 13 MSAs) nociceptors in hairy skin of pentobarbital sodium-anesthetized monkeys. An electrocutaneous search technique was used to locate the putative receptive fields of the MIAs. The response to mechanical and heat stimuli was determined before and after intradermal injection of a standard mixture of algesic/inflammatory mediators (bradykinin, histamine, serotonin, and prostaglandin E1). 3. All 25 MSAs, but only 65% of the MIAs, responded to the chemical stimulus. The A delta-fibers, both MSAs and responsive MIAs, and the responsive C-fiber MIAs gave a robust discharge. In contrast, the C-fiber MSAs (the conventional polymodal C-fiber nociceptors) exhibited a significantly weaker response. Three MIAs responded only to the chemical mixture and not to mechanical or heat stimuli. 4. Before injection of the chemical mixture, a significantly smaller proportion of C-fiber MIAs (50%) than of C-fiber MSAs (92%) responded to heat stimuli, whereas a similar proportion (38%) of A delta-fiber MIAs and MSAs were heat sensitive. 5. Approximately one-half of the MIAs and MSAs were sensitized to mechanical stimuli after the chemical injection, as manifest by a decreased threshold and/or an enlarged receptive field. 6. The chemical injection sensitized 90% of A delta-fiber MSAs, but only 8% of A delta-fiber MIAs, to heat stimuli. In contrast, 38% of C-fibers were sensitized. 7. In 14 fibers, the chemical stimulus resulted in sensitization to mechanical stimuli without sensitization to heat stimuli, or vice versa. This dissociated sensitized state suggests that the molecular mechanisms of sensitization to heat and mechanical stimuli differ. 8. In conclusion, a large proportion of primate cutaneous nociceptors respond to intradermal injection of algesic/inflammatory mediators and may also become sensitized to mechanical and/or heat stimuli.

Excitation of cutaneous afferent nerve endings in vitro by a combination of inflammatory mediators and conditioning effect of substance P.

A broad mixture of inflammatory mediators ("inflammatory soup") was used to investigate the responsiveness of primary afferents from rat hairy skin in an in vitro skin-saphenous nerve preparation. In addition, a conditioning effect of the tachykinin substance P on chemosensitivity of nociceptors was examined. Inflammatory soup (IS) was made up in synthetic interstitial fluid from bradykinin, serotonin, histamin and prostaglandin E2 (all 10(-5) M). In addition, the potassium and the hydrogen ion concentration (7 mM, pH 7.0) and the temperature (39.5 degrees C) were elevated. The latter agents, in a control solution, did not excite nociceptors (n = 5). IS was repeatedly superfused over the receptive fields for 5 min at 10 min intervals; substance P (SP 10(-6) and 10(-5) M) was applied during the last 5 min of the interval and during the subsequent IS stimulation. IS excited more than 80% of the mechano-heat sensitive ("polymodal") afferents with slowly conducting nerve fibres (n = 72), but none of the low-threshold mechanoreceptive slow and fast conducting units (n = 17). Slow conducting afferents with high mechanical threshold (n = 35) were weakly, and less frequently (< 20%), driven by IS. A majority, but not all, of the responsive units showed tachyphylaxis upon repeated IS application. None, however, lost its responsiveness completely. Conditioning heat stimulation (32-46.5 degrees C in 20 s) did not enhance the subsequent IS response, which may indicate that sensitizing substances normally released by a noxious heat stimulus were already contained in IS. No sensitization to mechanical (von Frey) or heat stimulation could be established in the period after the IS response had subsided and after the washout was completed, respectively. A short-lived sensitization may have been overlooked under these temporal restrictions. Conditioning SP in 10(-5) M but not in 10(-6) M concentration significantly increased the IS response of polymodal C fibres, by 58% on average (n = 14). SP did not excite the units. Comparing with previous data, we conclude that there is a significant synergism between inflammatory mediators, acting to induce more intense and more sustained discharge via many nociceptors than single mediators alone could achieve. Conditioning substance P can further enhance this algogenic action. Mechanisms of interaction and relative contributions of single substances remain to be elucidated.

Tonic descending influences on receptive-field properties of nociceptive dorsal horn neurons in sacral spinal cord of rat

1. Single-unit electrical activity has been recorded from 34 dorsal horn neurons in the sacral segments (S1-2) of the spinal cord in halothane-anesthetized rats. All of the neurons had cutaneous receptive fields (RFs) on the rat's tail. The neurons were classified according to their responses to both innocuous and noxious mechanical stimulation of their RFs. Twenty-five cells were driven by both innocuous and noxious skin stimulation (multireceptive or class 2), and 9 neurons were driven only by noxious skin stimulation (nocireceptive or class 3). 2. The RF size, mechanical threshold, and afferent input properties of these neurons were determined in the intact anesthetized and spinalized states. Reversible spinalization was achieved by cooling the cervical spinal cord to 4 degrees C. 3. The class 2 neurons had a mean RF size of 919.8 +/- 112.0 (SE) mm2 in the intact animal. Fourteen of the 25 class 2 cells had larger RFs in the spinal state (mean increase = 330.0 mm2, SE = 79.2) and so were under tonic descending inhibition. Five neurons, all with C-fiber input, had smaller RFs (mean decrease = 247.6 mm2, SE = 136.6) and higher mechanical thresholds in the spinal state and so were under tonic descending excitation. Six neurons were unaffected by spinalization. 4. Five class 3 neurons recorded in the superficial dorsal horn had small RFs in the intact animal (mean = 201.0 mm2, SE = 48.8) and showed little or no change in RF size on spinalization (mean increase = 33.4 mm2, SE = 16.7), but their mechanical thresholds did decrease, indicating weak tonic descending inhibition. In contrast, four class 3 neurons recorded in the deep dorsal horn had larger RFs in the intact animal (mean = 566.8 mm2, SE = 156.8), and were under strong tonic descending inhibition, because they had much larger RFs (mean increase = 461.0 mm2, SE = 68.3), lower mechanical thresholds, and stronger C-fiber afferent input in the spinal state. 5. We conclude that the majority of nociceptive dorsal horn neurons are subject to a net tonic descending control of their RF properties. The class 2 neurons in the deep dorsal horn appear to be a heterogeneous population, some cells being under tonic descending excitation and others under tonic descending inhibition. Class 3 cells can be separated into those located in the superficial dorsal horn, whose RF properties show very little change on spinalization, and those in the deep dorsal horn, whose RF properties change markedly on spinalization.(ABSTRACT TRUNCATED AT 400 WORDS)

Response properties and descending control of rat dorsal horn neurons with deep receptive fields

The study was designed to obtain information on the spinal processing of input from receptors in deep somatic tissues (muscle, tendon, joint). In anaesthetized rats, the impulse activity of single dorsal horn cells was recorded extracellularly. In a pilot series, the proportion of neurons responding to mechanical stimulation of deep tissues was determined: 46.7% had receptive fields in the skin only, 35.5% could only be driven from deep tissues (deep cells), and 17.7% possessed a convergent input from both skin and deep tissues (cutaneous-deep cells). In each category, neurons with low and high mechanical thresholds were encountered. Experiments employing a reversible cold block of the spinal cord showed that deep cells with high threshold were subject to a stronger descending inhibition than low-threshold deep cells. In cutaneous-deep neurons the input combination high-threshold cutaneous and high-threshold deep was the most frequent one (48.7% of the cutaneous-deep cells). In these presumably nociceptive cells the descending inhibition had a differential action in that the input from deep tissues was more strongly affected than was the cutaneous input to the same neuron. The recording sites of the neurons with deep input were located in the superficial dorsal horn and in and around lamina V. The results suggest that in the rat a considerable proportion of dorsal horn cells receives input from deep nociceptors and that this input is controlled by descending pathways in a rather selective way.

Sympathetic Activation of A-Delta Nociceptors

Primary afferent units in the saphenous nerve of cats, functionally identified as A-delta myelinated nociceptors, were tested for their responses to stimulation of the sympathetic trunk. The units were subdivided functionally into A-mechano-heat receptors (AMHs), which respond to both noxious heat and pressure, and high-threshold mechanoreceptors (HTMs), which respond only to pressure. No units of either subdivision were activated by sympathetic stimulation (SS) prior to noxious heating of their receptive fields. However, six of the seven AMH units with the highest mechanical thresholds (greater than 5 g von Frey) were activated by SS alone (10 Hz) after they had been sensitized by noxious heating of their receptive fields. Sensitized AMH units with lower mechanical thresholds (less than 5 g) were generally not activated by SS alone (1 of 22 units), and their responses to warming of their receptive fields were not altered by SS. The excitatory sympathetic action on AMH units was abolished by alpha- but not beta-andrenergic blockade in the two units tested. HTMs were unresponsive to SS even after repeated noxious heating of their receptive fields (15 units tested). The results of this study indicate that relatively high rates of sympathetic efferent activity (10 Hz) can induce firing in a small population of AMH receptors in damaged skin, specifically those units with high mechanical thresholds. This sympathetically evoked activity might trigger or exacerbate pain associated with skin damage; however, functional conclusions are difficult to draw, because of the scarcity of such units and the fact that the responses in some were brief and of low firing rates.

Muscle receptors with group IV afferent fibres responding to application of bradykinin

In 60 anaesthetized cats the discharge characteristics of single group IV afferent fibres from skeletal muscle at rest, during local mechanical stimulation of the muscle, and in response to injections of bradykinin have been studied. 250 group IV fibres from the gastrocnemius-soleus muscle have been identified by their conduction velocity. Of these fibres 121 have been recorded from the dorsal root and 129 from the muscle nerve. A resting discharge was present in 52% of the dorsal root fibres and in 57% of the fibres recorded peripherally. Out of 203 units subjected to local mechanical stimulation of the muscle 9 responded to light, innocuous pressure; 129 fibres required strong, presumably noxious stimulation to be excited. The rest of 65 fibres could not be activated by the mechanical stimuli used. Intraarterial injection of bradykinin excited 88 out of 184 group IV fibres. Intramuscular injection of bradykinin was also found to be an effective stimulus. External application of bradykinin to the intact and to the dissected muscle nerve regularly had no excitatory effect on fibres being sensitive to intraarterially administered bradykinin. Injections of vasoactive drugs (nylidrine, noradrenaline) failed to affect the activity of group IV fibres responding to bradykinin. It is concluded that bradykinin is a potent stimulant for the intramuscular endings of afferent group IV fibres; the effective concentration lying within the range observed in pathologically altered tissues. This sensitivity to bradykinin together with a high mechanical threshold suggests that muscular group IV afferent units participate in the reception of muscular pain.

Response patterns of cutaneous mechanoreceptors in the domestic duck

1. 1. Cutaneous mechanoreceptors in the domestic duck, Anas platyrhynchos, were classified as follows. 2. 2. Down feather units were quickly adapting with large receptive fields and low mechanical thresholds. 3. 3. Touch receptors possessed localized receptive fields, medium to high mechanical thresholds and a range of adaptation rates. 4. 4. Slowly adapting units with high thresholds and diffuse receptive fields were presumed pressure or nociceptive receptors. 5. 5. Vibration sensitive units followed 1 : 1 up to 400–800 c/sec, giving steady responses at 600–1000 c/sec. Individually exposed Herbst corpuscles were shown to respond similarly to vibration.

An electrophysiological analysis of cutaneous mechanoreceptors in a snake

1. 1. A systematic analysis of mechanoreceptors in skin of the snake Pseudechis porthyriacus revealed several response patterns. Some units adapted rapidly to an applied stimulus and others gave a maintained discharge to prolonged stimulation. A few receptors we encountered which had an intermediate adaptation rate. 2. 2. The majority of rapidly adapting receptors had a relatively high mechanical threshold, were insensitive to high-frequency vibrational stimuli and had restricted receptive fields that overlapped extensively. 3. 3. The slowly adapting receptors were of low mechanical threshold making it difficult to map their receptive fields. Their response pattern could be modified by altering skin temperature.