Biomedical subjects

R D Treede

Publications and source records attributed to R D Treede.

At least 37 records · Page 2Linked to original sources

PubMed1998

[Pathophysiology and diagnosis in patients with sympathetically dependent pain].

Chronic pain in a distal extremity that is accompanied by autonomic dysfunction in the same region is taken to indicate reflex sympathetic dystrophy. Typically, hyperalgesia to light touch is present in addition to the spontaneous pain. The absence of heat hyperalgesia indicates that the underlying mechanism is central rather than peripheral sensitization. This mechanism is similar to that of secondary hyperalgesia in the intact skin surrounding an injury site. Sympathetically maintained pain (SMP) is diagnosed, when these sensory symptoms are reversible under sympathetic blockade. SMP is not due to hyperactivity of sympathetic efferents but to receptor supersensitivity, probably by overexpression of alpha(1)-adrenergic receptors on nociceptive primary afferents. This way normal levels of norepinephrine can cause pathological spontaneous activity of nociceptors which maintains the central sensitization. Chronic burning pain and cutaneous hyperalgesia may also be independent of the sympathetic innervation of the skin. In this case, central sensitization is maintained by other mechanisms. A role of the sympathetic nervous system in the pathogenesis of pain cannot be deduced simply from the simultaneous presence of sensory and autonomic clinical signs and symptoms. Therefore, sympathetic blockade in a patient initially is a diagnostic procedure, aiming to demonstrate the presence of the symptom SMP. Therapeutic blockade is only indicated after this demonstration. For the substantial number of patients with sympathetically independent pain, other treatment modalities are needed which may for example attack central sensitization.

English Abstract↗

PubMed1998

Characterization of blink reflex interneurons by activation of diffuse noxious inhibitory controls in man.

The blink reflex consists of an early, pontine R1-component and a late, medullary R2-component. R1 and R2 can be evoked by innocuous stimuli, but only the R2 also by painful heat, suggesting that the R2 is mediated by wide dynamic range neurons (WDR) of the spinal trigeminal nucleus. Remote noxious stimuli suppress the activity in WDR neurons via activation of diffuse noxious inhibitory controls (DNIC), whereas low-threshold mechanoreceptive neurons (LTM) are unaffected. In order to characterize the trigeminal interneurons of R1 and R2 we investigated the modulation of the blink reflex by remote painful heat. The blink reflex was elicited in 11 healthy subjects by innocuous electrical pulses applied to the left supraorbital nerve. The remote, painful heat stimuli were applied by a Peltier type thermode to the left volar forearm. Remote painful heat of 44 to 46 degreesC significantly suppressed the R2 by 15% (p<0.01), while the R1 remained unchanged. These results provide further evidence that the R2 is mediated by medullary WDR neurons and the R1 by pontine LTM neurons.

Adult↗

PubMed1998

The Hoffmann reflex of human plantar foot muscles.

Electrical stimulation of the tibial nerve in the popliteal fossa evoked an M wave (10.9 ms) and a late reflex response (38.1 ms) in the plantar foot muscles of all 10 volunteers. The late response had a somewhat lower electrical threshold than the corresponding M wave (8.5 versus 9 mA), and reached a maximum of amplitude when the stimulus intensity was increased, but was strongly suppressed by further increased intensity. A more distal stimulation of the tibial nerve at the ankle shortened the onset latency of the M wave and lengthened that of the late response. The reflex was facilitated by activation of synergists and inhibited by activation of antagonists. We showed that the late response was contaminated neither by volume conducted activity from the soleus muscle, as shown by intramuscular recordings from the abductor hallucis muscle, nor by a F wave, as shown by double stimulation. In summary, we conclude that this late response in human plantar foot muscles corresponded to an H reflex, which may be used to assess alterations of distal motoneuronal excitability.

Adult↗

PubMed1998

Brain electrical source analysis of primary cortical components of the tibial nerve somatosensory evoked potential using regional sources.

Tibial nerve somatosensory evoked potentials (SEPs) show higher amplitudes ipsilateral to the side of stimulation, whereas subdural recordings revealed a source in the foot area of the contralateral hemisphere. We now investigated this paradoxical lateralization by performing a brain electrical source analysis in the P40 time window (34-46 ms). The tibial nerve was stimulated behind the ankle (8 subjects). On each side, 2048 stimuli were applied twice. SEPs were recorded using 32 magnetic resonance imaging (MRI)-verified electrode positions (bandpass 0.5-500 Hz). In each case, the P40 amplitude was higher ipsilaterally (0.45 +/- 0.14 microV) than contralaterally (-0.49 +/- 0.16 microV). The best fitting regional source, however, was always located in the contralateral hemisphere with a mean distance of 8.2 +/- 4.3 mm from the midline. The positivity pointed ipsilaterally shifting from a frontal orientation (P37) to a parietal direction (P40). The P40 dipole moment was 2.5 times stronger than the dipole moment of P37, which makes P40 most prominent in EEG recordings. However, with its oblique dipole orientation compared to the tangential P37 dipole, it is systematically underestimated in MEG. Dipole orientations explained interindividual variability of scalp potential distribution. SEP amplitudes were smaller when generated in the dominant (left) hemisphere. This is explained by deeper located sources (5.4 +/- 1.6 mm) with a more tangential orientation (delta theta = 17.5 +/- 2.3 degrees) in the left hemisphere.

Adult↗

PubMed1998

Secondary hyperalgesia and perceptual wind-up following intradermal injection of capsaicin in humans.

Wind-up and secondary hyperalgesia both are related to central sensitization, but whereas the former is explained by homosynaptic facilitation, the latter is due to heterosynaptic facilitation. To investigate possible interactions between both types of facilitation, we tested for alterations of perceptual wind-up in the secondary hyperalgesic skin zone adjacent to a capsaicin injection with light touch (by a cotton wisp) and punctate stimuli (calibrated von Frey hairs and pin pricks). Temporal summation of pain sensation (perceptual wind-up) was only observed with a clearly noxious stimulus (pin prick) presented at a repetition frequency of 0.6 s(-1), but not 0.2 s(-1). Pain ratings to trains of pin pricks reached a plateau after 3-4 repetitions, which was 1.65 times the initial rating ('wind-up ratio'). Injection of capsaicin induced a tenderness to mechanical stimuli in adjacent uninjured skin (secondary hyperalgesia), including hyperalgesia to light touch (allodynia) and hyperalgesia to punctate stimuli. Hyperalgesia to punctate stimuli was characterized by a leftward shift of the stimulus response function, corresponding to a decrease in pain threshold and an increase of painfulness of suprathreshold stimuli by a factor of 3-4. After capsaicin, the difference between the ratings of the first and last stimuli of trains of pin pricks was increased, but the ratio was unchanged. This behavior is equivalent to an increase in effective stimulus intensity, and could be mimicked by increasing the pin prick force from 20 mN to 40 and 80 mN in normal skin. Thus, the leftward shift of the stimulus response function fully accounts for all alterations of pain sensitivity to punctate stimuli in the zone of secondary hyperalgesia. We conclude that when the gain of spinal transmission was changed in secondary hyperalgesia, the gain of wind-up remained unchanged. These findings indicate that secondary hyperalgesia (heterotopic facilitation) and wind-up of pain sensation (homotopic facilitation) are independent phenomena.

Adolescent↗

PubMed1998

Convergence of nociceptive and non-nociceptive inputs onto spinal reflex pathways to the tibialis anterior muscle in humans.

The interaction of low-threshold mechanoreceptive and nociceptive inputs onto spinal neurones probably plays a major role in the pathophysiology of the clinical sign of allodynia. This phenomenon was investigated by modulation of the early component of the flexor reflex (FR) in the tibialis anterior (TA) muscle, elicited by electrical stimulation of the medial plantar nerve at the sole of the foot, by homotopically applied painful heat in humans. This early reflex with an electrical threshold of 2.7-fold the detection threshold and a mean afferent conduction velocity of 49 m s-1 is a non-nociceptive FR. When applying conditioning painful heat (46 degrees C) to the sole of the foot this reflex was significantly increased by a factor of 3.4 (non-painful electrical stimuli; n = 5) and 2.0 (painful electrical stimuli; n = 11). The onset latencies were significantly shortened from 74.2 to 64.0 ms and 69.6 to 63.7 ms, respectively. A late nociceptive FR was also facilitated. While the Hoffmann reflex (HR) in the TA muscle was nearly abolished by painful heat, the HR in the soleus (SO) muscle remained unchanged. These data suggest a convergence of low-threshold mechanoreceptive and nociceptive inputs onto spinal reflex pathways in humans, probably at an interneuronal level in humans.

Adult↗

PubMed1998

Myelinated mechanically insensitive afferents from monkey hairy skin: heat-response properties.

To compare the heat responses of mechanically sensitive and mechanically insensitive A-fiber nociceptors, an electrical search technique was used to locate the receptive fields of 156 A-fibers that innervated the hairy skin in the anesthetized monkey (77 A beta-fibers, 79 A delta-fibers). Two-thirds of these afferents were either low-threshold mechanoreceptors (n = 91) or low-threshold cold receptors (n = 11). Nine A beta-fibers and 41 A delta-fibers were cutaneous nociceptors, and four A delta-fibers innervated subcutaneous tissue. The majority of cutaneous A-fiber nociceptors were heat sensitive (43/50 = 86%). Heat-insensitive cutaneous A-fiber nociceptors consisted of one cold nociceptor, three silent nociceptors, and three high-threshold mechanoreceptors. Two types of response were observed to an intense heat stimulus (53 degrees C, 30 s). Type I (n = 26) was characterized by a long latency (mean: 5 s) and a late peak discharge (16 s). Type II (n = 17) was characterized by a short latency (0.2 s) and an early peak discharge (0.5 s). Type I fibers exhibited faster conduction velocities (25 vs. 14 m/s) and higher heat thresholds (> 53 vs. 47 degrees C, 1-s duration) than type II fibers. The possibility that the type I heat response was a result of sensitization was tested in three fibers by determining the heat threshold to 30-s duration stimuli (42-46 degrees C). For this long stimulus duration heat thresholds were reproducible across multiple runs, and the threshold to the 1-s duration stimulus was not altered by these tests. Thus fibers with a type I heat response were not high-threshold mechanoreceptors that developed a heat response through sensitization. Fibers with a type II heat response had significantly higher mechanical thresholds (median: 15 bar) than fibers with a type I heat response (5 bar). This finding accounts for the observation that type II heat responses were infrequently observed in earlier studies wherein the search technique depended on mechanical responsiveness. Fibers with a type II response exhibited a graded response to heat stimuli, marked fatigue to repeated applications of heat stimuli, and adaptation to sustained heat stimuli similar to that seen in C-fiber nociceptors. First pain sensation to heat is served by type II A-fiber nociceptors that are mechanically insensitive. Type I A-fiber nociceptors likely signal pain to long-duration heat stimuli and may signal first pain sensation to mechanical stimuli.

Action Potentials↗

PubMed1997

Nociceptive masseter inhibitory reflexes evoked by laser radiant heat and electrical stimuli.

Electrical stimulation of the mental nerve evokes two suppression periods SP1 and SP2 in masseter muscle activity bilaterally. In order to investigate a possible nociceptive origin of the suppression periods, we compared the reflex responses evoked by electrical stimulation and by selective activation of nociceptors in hairy skin using painful infrared laser stimuli. The SP was elicited during more than 90% maximal voluntary contraction. Thresholds for detection, pain, and SP in the mental nerve area were determined by the method of limits. A suppression period was evoked by laser stimuli in nine of ten subjects bilaterally. The mean onset latency was 46.9 ms, the mean duration 58.9 ms. The electrical threshold of SP1 (9 mA) was 7.7 x I(0), about 20% smaller than I(P), and significantly higher than I(SP2) (4.7 mA). The onset latencies and durations were 11.7 ms and 21 ms for SP1, and 45 ms and 42.7 ms for SP2 (stimulus intensity 2 x I(P)). The mean difference in onset latencies between laser SP and electrically evoked SP1 was 35.1 +/- 6.2 ms, which closely matches the nociceptor response latency to a laser heat pulse. Based on the threshold and the onset latency we conclude that at least SP1 and laser SP are nociceptive in origin and mediated by group III fibers.

Adult↗

PubMed1997

Coexpression of heat-evoked and capsaicin-evoked inward currents in acutely dissociated rat dorsal root ganglion neurons.

Noxious heat is able to activate heat-sensitive nociceptors in the skin very rapidly, but little is known about the mechanisms by which heat is transduced. We used the whole-cell patch-clamp technique to study the effects of noxious heat and capsaicin on freshly dissociated rat dorsal root ganglion neurons in vitro. Using temperatures between 41 degrees C and 53 degrees C, 8 of 19 small neurons (phi < or = 30 microm) exhibited a heat-evoked inward current. All heat-sensitive neurons tested were also capsaicin-sensitive. Moreover, the heat response tended to be enhanced after capsaicin (360 +/- 150 pA versus 125 +/- 45 pA, P < 0.1, n = 7). Two of five heat-insensitive neurons were excited by capsaicin; both neurons developed a heat response after capsaicin. Large neurons (phi > 30 microm) did not respond to heat (0/7), and were not sensitive to capsaicin either. These findings indicate that heat stimuli may directly activate capsaicin-sensitive primary nociceptive afferents.

Animals↗

PubMed1997

Median and tibial nerve somatosensory evoked potentials: middle-latency components from the vicinity of the secondary somatosensory cortex in humans.

The topography of the middle-latency N110 after radial nerve stimulation suggested a generator in SII. To support this hypothesis, we have tried to identify a homologous component in the tibial nerve SEP (somatosensory evoked potential). Evoked potentials following tibial nerve stimulation (motor + sensory threshold) were recorded with 29 electrodes (bandpass 0.5-500 Hz, sampling rate 1000 Hz). For comparison, the median nerve was stimulated at the wrist. Components were identified as peaks in the global field power (GFP). Map series were generated around GFP peaks and amplitudes were measured from electrodes near map maxima. With median nerve stimulation, we recorded a negativity with a maximum in temporal electrode positions and 106 +/- 12 ms peak latency (mean +/- SD), comparable to the N110 following radial nerve stimulation. After tibial nerve stimulation the latency of a component with the same topography was 131 +/- 11 ms (N130). Both N110 and N130 were present ipsi- as well as contralaterally. Amplitudes were significantly higher on the contralateral than the ipsilateral scalp for both median (3.1 +/- 2.4 microV vs. 1.7 +/- 1.6 microV) and tibial nerve (1.9 +/- 1.2 microV vs. 0.6 + 1 microV). The topography of the N130 can be explained by a generator in the vicinity of SII. The latency difference between median and tibial nerve stimulation is related to the longer conduction distance (cf. N20 and P40). The smaller ipsilateral N130 is consistent with the bilateral body representation in SII.

Adult↗

PubMed1996

Heat-evoked vasodilatation in human hairy skin: axon reflexes due to low-level activity of nociceptive afferents.

1. Spreading vasodilatation of the axon reflex type was evoked by contact heat stimulation of the hairy skin in the human forearm (13.3 cm2 stimulus area) and was detected by laser Doppler flowmetry at 8, 19 and 30 mm distance. 2. From a base temperature of 35 degrees C, rapidly rising short heat stimuli (4 degrees C s-1, 2 s plateau) elicited vasodilatation at an average threshold of 39.4 degrees C. For slowly rising sustained heat stimuli (64 s duration) the average threshold was 39.6 degrees C (n.s.) Laser Doppler flowmetry revealed a rapid onset within about 4 s, a long duration of several minutes beyond the end of the stimulus, and a rapid spread of vasodilatation to remote skin areas. These characteristics are typical for vasodilatation by an axon reflex of nociceptive afferents. 3. Axon reflex thresholds matched the lower range of C fibre nociceptor heat thresholds. Thermal stimuli that were adjusted to elicit about half-maximal phasic responses in warm fibres (steps from 30 to 35 degrees C), but were below the range of C fibre nociceptor thresholds, did not cause any vasodilatation. 4. Pain thresholds were higher than axon reflex thresholds for both rapidly and slowly rising heat stimuli and strongly depended on the stimulus pattern (40.1 degrees C for rapidly rising stimuli and > 43 degrees C for slowly rising stimuli). This observation is consistent with recent reports that the phasic response of nociceptive afferents is essential to overcome the summation requirements at central synapses. 5. In conclusion, axon reflex vasodilatation in response to heat stimuli in the hairy skin of humans is elicited by activation of heat-sensitive nociceptors, even in the absence of a conscious perception of heat pain. The dissociation of pain and vasodilatation thresholds supports the concept of two operating ranges of primary nociceptive afferents. Warm fibres do not contribute to axon reflex vasodilatation in the hairy skin of the human forearm. Release of vasoactive peptides by nociceptive primary afferents may also contribute to local heat-evoked vasodilatation at temperatures above 40 degrees C.

Adolescent↗

PubMed1996

Laser-evoked potentials after painful hand and foot stimulation in humans: evidence for generation of the middle-latency component in the secondary somatosensory cortex.

The vertex potential (N2, P2) of the laser-evoked potential (LEP) is preceded by a small negativity (N1). The role of the secondary somatosensory cortex (SII) in generation of the N1 is established for the upper but not for the lower limb. We therefore investigated the N1 after painful radiant heat stimulation of hand and foot dorsum in 22 subjects. LEPs were recorded from the scalp with midline and temporal electrodes. After hand stimulation N1 was maximal in the contralateral temporal lead (mean peak latency 156 +/- 23 ms). After foot stimulation N1 was maximal in the same lead (200 +/- 22 ms). In the ipsilateral temporal lead, N1 appeared significantly smaller and later. N2 and P2 were maximal in midline electrodes for both stimulus sites. The latency shift between hand and foot stimulation was identical for all three components. These results suggest a contribution of temporo-parietal cortex (e.g. SII) to the N1 generation for stimulation of upper and lower limb.

Adult↗

PubMed1996

Laser-evoked potentials: exogenous and endogenous components.

The aim of this study was to distinguish the exogenous component (related to the physical properties of the stimulus) and the endogenous component (reflecting event-related cognitive processing) of the laser-evoked potential (LEP). Short painful radiant heat pulses generated by a CO2-laser were applied to the dorsum of the right and left foot. LEPs were recorded with 5 scalp electrodes in the midline versus linked earlobes in 26 healthy subjects. In order to identify the exogenous component, the LEP was recorded during a standardised distraction task (reading a short story). To identify the endogenous component P3 for the LEP, a 2-stimulus oddball paradigm was used (20% probability of targets). When the task of the oddball paradigm consisted of pressing a button, a movement-related long-latency negativity (N 1200) was recorded in frontal leads that was absent in a counting task. The LEP of targets, frequent non-targets and during distraction was dominated by a single large positivity. The amplitude of this positivity was task-dependent and increased the more attention the subject payed to the laser stimuli (distraction < neutral < non-target < target). The laser-evoked positivity during distraction had a peak latency of about 400 msec (P400) and a maximum amplitude at the vertex, which was independent of inter-stimulus interval. The P3 following laser stimulation had a significantly later peak at about 570 msec (P570) and a different scalp topography with a parietal maximum. Its amplitude decreased when the interstimulus interval was reduced from 10 to 6 sec. Under neutral instructions, the LEP positivity consisted of a superposition of both the exogenous P 400 and the endogenous P570.

Adult↗

PubMed1996

Paradoxical heat sensation in patients with multiple sclerosis. Evidence for a supraspinal integration of temperature sensation.

Temperature thresholds were determined in 16 patients with probable or definite multiple sclerosis, in six patients with possible but unconfirmed multiple sclerosis and in 34 healthy subjects, using the method of limits and the thermal sensory limen (TSL) of the MarStock technique. A significant proportion of the patients had thresholds outside the 2.5 SD range for normal subjects, both for warmth detection threshold and TSL. In addition, 10 patients with probable or definite multiple sclerosis and one patient with possible multiple sclerosis reported a paradoxical heat sensation, i.e. a sensation of warmth elicited by a cold stimulus. This illusion was almost exclusively observed with the alternating warm and cold stimuli of the TSL procedure. In contrast to experimental nerve block or peripheral demyelinating neuropathy, where paradoxical heat sensation has been described by various authors, in the patients with multiple sclerosis the demyelination sites were located in the central nervous system. The observation that multiple sclerosis patients had paradoxical heat sensation in addition to threshold abnormalities supports the view that supraspinal sites are important for the integration of temperature sensation.

Adult↗

PubMed1996

Recovery from brain-stem lesions involving the nociceptive pathways: comparison of clinical findings with laser-evoked potentials.

Dissociated sensory impairment in brain-stem disorders suggests a lateral lesion involving the spinothalamic tract. Evoked potential studies of the somatosensory system with standard electrical stimulation (SEP) generally fail to establish objective correlates of such sensory deficits, because electrical stimuli predominantly activate large myelinated fibers that project into the medial lemniscal system. In contrast, laser-evoked potentials (LEPs), in response to brief radiant heat pulses, stimulate nociceptive afferents of the superficial skin and allow evaluation of thin fiber and spinothalamic tract function. We describe the recovery of deficits in pain sensitivity in five patients with isolated lateral brain-stem lesions that could be successfully monitored by LEP recordings in the acute stage and after intervals ranging from 7 months to 4 years. Upon first examination, LEPs were abnormal on the affected body side in all five cases of lateral medullary syndrome, irrespective of whether the etiology was vascular or inflammatory. The degree of recovery of pain sensitivity upon reexamination was reflected by the extent of normalization of the LEP. A control patient with vascular pontine lacunar stroke had normal LEPs on both sides, suggesting preserved spinothalamic conduction. The peak-to-peak amplitude of the main LEP component (N250-P400) correlated significantly with clinical pain sensitivity scored by standardized sensory testing (r = 0.76, p < 0.01). In contrast, early and late SEPs, after standard electrical median or tibial nerve stimulation, were normal in all patients, consistent with their intact mechanosensitivity. In conclusion, LEP studies allow the status of nociceptive function to be objectively and reliably documented on repeated examinations and therefore provide a useful supplement to multimodal sensory assessment in brain-stem disorders.

Adult↗

PubMed1995

Response of C fibre nociceptors in the anaesthetized monkey to heat stimuli: estimates of receptor depth and threshold.

1. Responses to ramped or stepped temperature stimuli were obtained from fifty-three cutaneous C fibre mechano-heat nociceptors (CMHs) in the hairy skin of the pentobarbitone-morphine anaesthetized monkey. A three-layer heat transfer model was developed to describe the temperature distribution within the skin and to estimate receptor depth and heat threshold. 2. Surface heat threshold, defined as the surface temperature when the first action potential occurs, increased as: (a) the rate of temperature rise for the ramped stimuli increased from 0.095 to 5.8 degrees C s-1; (b) the duration of stepped heat stimuli decreased from 30 to 1 s; and (c) the base temperature of stepped heat stimuli decreased from 38 to 35 degrees C. These results suggest that the heat threshold for CMHs is determined by the temperature at the depth of the receptor. 3. Receptor depth estimates from responses to ramped stimuli ranged from 20 to 570 microns with a mean of 201 microns. The estimated mean receptor heat threshold was 40.4 +/- 2.2 degrees C (+/- S.D.). No correlation was observed between depth and thermal or mechanical threshold. The average receptor depth and threshold, estimated from the responses to stepped heat stimuli, were 150 microns and 40.2 degrees C, respectively. 4. We conclude that: (a) the receptor endings of CMHs occur in the epidermis and dermis; (b) temperature at the level of the receptor determines threshold; (c) temperature at the receptor ending is much lower than skin surface temperature at threshold; and (d) the tight distribution of receptor heat thresholds suggests a uniform transducer mechanism for heat in CMHs.

Animals↗

PubMed1995

Response of C fibre nociceptors in the anaesthetized monkey to heat stimuli: correlation with pain threshold in humans.

1. Ramped heat stimuli were used to compare the effects of rate of temperature change on the responses of monkey nociceptors and on heat pain threshold in human subjects. Recordings were made from twenty-five cutaneous C fibre mechano-heat nociceptors (CMHs) innervating the hairy skin in the anaesthetized monkey. Heat pain thresholds were determined on the volar forearm of eight human subjects using a converging staircase technique. 2. The heat pain threshold decreased as stimulus ramp rate increased. In contrast, the CMH heat threshold, defined as the surface temperature at which the first action potential occurred, increased as stimulus ramp rate increased. Thus, the properties of the heat stimulus that dictate heat pain threshold are different from the properties of the heat stimulus that govern the initiation of a response in nociceptors. 3. Peak discharge frequency of CMHs during the heat ramp increased with stimulus ramp rate. Heat pain threshold was correlated with achievement of a minimum discharge rate in nociceptors (0.5 Hz), rather than with the threshold for action potential initiation.

Action Potentials↗

PubMed1995

Evidence for two different heat transduction mechanisms in nociceptive primary afferents innervating monkey skin.

1. Mechano- and heat-sensitive A fibre nociceptors (AMHs) and C fibre nociceptors (CMHs) in hairy skin (forty-six AMHs and twenty-one CMHs) and in glabrous skin (fifty-nine AMHs and ten CMHs) of anaesthetized monkeys were tested with a 30 s, 53 degrees C heat stimulus, delivered by a laser thermal stimulator (0.1 s rise time, 7.5 mm diameter). 2. Two types of heat response were observed in hairy skin AMHs. Type I AMHs had a peak discharge towards the end of the stimulus, response latencies to heat of up to several seconds, a median heat threshold greater than 53 degrees C, and a mean conduction velocity of 25 m s-1 (n = 33). Type II AMHs had a peak discharge within 1-3 s, a mean response latency of 120 ms, a median heat threshold of 46 degrees C, and a mean conduction velocity of 15 m s-1 (n = 13). Type I AMH fibres were sensitized to heat, whereas heat responses of type II AMHs were suppressed following the intense heat stimulus. 3. In glabrous skin, only type I AMHs were found. The absence of type II AMHs is consistent with the absence of first pain to heat in glabrous skin. 4. C fibre nociceptors in hairy skin had a peak discharge near stimulus onset, a mean response latency of 100 ms and a median heat threshold of 41 degrees C. Heat responses of CMHs in glabrous skin were not significantly different from those in hairy skin. 5. Only type II AMHs had response latencies that were short enough to explain first pain to heat. Heat thresholds of type II AMHs were significantly higher than those of CMHs. 6. These results suggest two different heat transduction mechanisms in nociceptive afferents. For one, heat energy is quickly transduced into action potentials, and the peak discharge is reached soon after stimulus onset. For the other, the transduction of heat is distinctly slower, and the peak discharge occurs near the end of the stimulus. Chemically mediated sensitization may be involved in the second transduction mechanism.

Animals↗