Innocuous Thermal Stimulation Research Articles

A Comparison of Functional Connectivity in the Human Brainstem and Spinal Cord Associated with Noxious and Innocuous Thermal Stimulation Identified by Means of Functional MRI.

The somatosensory system is multidimensional and processes important information for survival, including the experience of pain. The brainstem and spinal cord serve pivotal roles in both transmitting and modulating pain signals from the periphery; although, they are studied less frequently with neuroimaging when compared to the brain. In addition, imaging studies of pain often lack a sensory control condition, failing to differentiate the neural processes associated with pain versus innocuous sensations. The purpose of this study was to investigate neural connectivity between key regions involved in descending modulation of pain in response to a hot, noxious stimulus as compared to a warm, innocuous stimulus. This was achieved with functional magnetic resonance imaging (fMRI) of the brainstem and spinal cord in 20 healthy men and women. Functional connectivity was observed to vary between specific regions across painful and innocuous conditions. However, the same variations were not observed in the period of anticipation prior to the onset of stimulation. Specific connections varied with individual pain scores only during the noxious stimulation condition, indicating a significant role of individual differences in the experience of pain which are distinct from that of innocuous sensation. The results also illustrate significant differences in descending modulation before and during stimulation in both conditions. These findings contribute to a deeper understanding of the mechanisms underlying pain processing at the level of the brainstem and spinal cord, and how pain is modulated.

Immediate effects of noxious and innocuous thermal stimulation on brain activation in patients with stroke.

Case-control studies have shown that noxious thermal stimulation (TS) can improve arm function in patients with stroke. However, the neural mechanisms underlying this improvement are largely unknown. We explored functional neural activation due to noxious and innocuous TS intervention applied to the paretic arm of patients with stroke. Sixteen participants with unilateral cortical infarctions were allocated to one of two groups: noxious TS (8 patients; temperature combination: hot pain 46°C to 47°C, cold pain 7°C–8°C) or innocuous TS (n = 8; temperature combination: hot 40°C–41°C, cold 20°C–21°C). All subjects underwent fMRI scanning before and after 30 min TS intervention and performed a finger tapping task with the affected hand. Immediate brain activation effects were assessed according to thermal type (noxious vs. innocuous TS) and time (pre-TS vs post-TS). Regions activated by noxious TS relative to innocuous TS (P < .05, adjusted for multiple comparisons) were related to motor performance and sensory function in the bilateral primary somatosensory cortices, anterior cingulate cortex, insula, thalamus, hippocampus and unilateral primary motor cortex, secondary somatosensory cortex at the contralateral side of lesion, and unilateral supplementary motor area at the ipsilateral side of lesion. Greater activation responses were observed in the side contralateral to the lesion, suggesting a significant intervention effect. Our preliminary findings suggest that noxious TS may induce neuroplastic changes unconstrained to the local area.Trial registration: NCT01418404

Modulation of Itch by Localized Skin Warming and Cooling.

Skin thermal changes modulate itch sensitivity. However, the mechanisms of this modulation are still unclear. Using mouse models of acute and chronic itch, we investigated whether local innocuous thermal stimulation of the skin alters itch sensitivity and if blockade of thermosensitive transient receptor potential (TRP) channels can reduce these changes. Localized thermal changes were achieved by placing a thermal probe in contact with the back skin for 30 s. Warming the skin significantly increased serotonin-evoked scratching and spontaneous scratching in the ovalbumin model of atopic dermatitis but decreased histamine-evoked scratching. These changes were blocked by a TRPV4 antagonist. Cooling the skin significantly increased serotonin-evoked scratching but reduced histamine-evoked scratching. The increase in serotonin-evoked scratching, but not the reduction of histamine-evoked scratching, was blocked by TRPM8 antagonism. Chloroquine-evoked scratching was unaffected by either warming or cooling. Our data indicate that different itch signaling pathways are differentially modulated by skin thermal changes.

No Difference Between Noxious and Innocuous Thermal Stimulation on Motor Recovery of Upper Extremity in Patients With Acute Stroke: A Randomized Controlled Trial With 6-Month Follow-up

BackgroundThermal stimulation (TS) has been developed and incorporated into stroke rehabilitation. However, whether noxious and innocuous TS induce the same effects on motor function recovery after stroke is still unknown. A comparative study of different temperature combination regimens is needed. ObjectiveTo compare the short- and long-term effectiveness between noxious and innocuous TS on motor recovery of upper extremity in patients with acute stroke. DesignRandomized, controlled trial with concealed allocation, intention-to-treat analysis and blinded outcome assessors. SettingA university hospital rehabilitation department in Taiwan. ParticipantsA total of 79 patients with acute ischemic stroke were recruited. The majority had moderate to severe motor impairment of the upper extremity (UE). InterventionIn addition to traditional rehabilitation, the experimental group (n = 39) underwent noxious TS (heat pain 46-47°C/cold pain 7-8°C), and the control group (n = 40) received innocuous TS (heat 40-41°C/cold 20-21°C). TS intervention was applied for 30 minutes once per day and for a total of 20-24 times during hospital stay. A custom-made TS instrument, comprising 2 thermal stimulators and their respective thermal pads constructed in a closed-loop system, was used. OutcomesThe Fugl-Meyer upper extremity score (the primary outcome), Action Research Arm Test, Motricity Index, Barthel Index, and modified Ashworth scale (the secondary outcomes) were administered by a blinded assessor at baseline, post–12th TS, post-intervention, 1-month, and 6-month follow-ups. ResultsNo significant differences between groups were found on the primary outcome at postintervention and follow-up assessments. At 1-month follow-up, the innocuous group showed a small effect (partial η2 = 0.02) that was greater than that of the noxious group, but that effect was eliminated at 6 months. Both groups presented significant within-group improvements over time (both P < .001). ConclusionsCombining noxious TS with traditional rehabilitation did not yield better short-term or long-term results than combining innocuous TS with traditional rehabilitation on UE functional recovery for individuals with acute stroke. Level of EvidenceII

(313) The insula's functional connectivity to the default mode network is uniquely altered by pain perception

Multiple studies across imaging modalities suggest the insula has a key role in pain processing. Recent work using functional connectivity MRI (fcMRI) during painful and innocuous thermal stimulation demonstrated anatomically different connectivity: the anterior insula (aIns) was more strongly correlated to the anterior cingulate cortex (ACC), while the posterior insula (pIns) better correlated to the primary somatosensory (S1) and motor (M1) cortices. Similarly, our prior work showed altered connectivity of the pIns to default mode network (DMN), and the posterior cingulate cortex (PCC) in particular, during painful acute electric nerve stimulation versus rest.

Effect of thermal stimulation on corticomotor excitability in patients with stroke.

This study examined the immediate effects of noxious and innocuous thermal stimulation intervention on corticomotor excitability for the paretic arm in patients with stroke. Sixteen patients with stroke for more than 3 mos were randomly assigned into the experimental and control groups. All participants received the thermal stimulation protocol on the affected arm for 30 mins. The experimental group received noxious heat (46°C-47°C) and cold (7°C-8°C) stimuli, and the control group received innocuous heat (40°C-41°C) and cold (20°C-21°C) stimuli. Corticomotor excitability was assessed to measure the motor threshold, size of cortical motor output map, and mean motor evoked potentials for the abductor pollicis brevis by focal transcranial magnetic stimulation before and after 30 mins of thermal stimulation intervention program. The findings of transcranial magnetic stimulation revealed a significant increase in map size of the affected hemisphere and mean motor evoked potentials in the experimental group. Moreover, significant differences in the change values of map size (7.0 [7.9] for the experimental group vs. -1.7 [2.9] for the control group, P = 0.03) and mean (SD) motor evoked potentials (0.4 [8.9] mV for the experimental group vs. -0.1 [0.1] mV for the control group, P = 0.03) were found. The preliminary results suggest that the noxious 30 mins of thermal stimulation intervention induced neurophysiologic changes in the motor cortex of the lesioned hemisphere.

Thermoreceptive neurons in the dorsal portion of the trigeminal principal nucleus in rats

The dorsal margin of the trigeminal principal nucleus (PV) contains neurons responsive to innocuous thermal stimulation of the tongue and maybe a thermal relay (Hayama and Hashimoto, 2011). The present electrophysiological study examined whether PV thermoreceptive neurons project to the thalamus and investigated response properties to cold (20°C) or warm (40°C) stimulation of the tongue. Twenty-three thermoreceptive neurons were identified in the dorsal portion of the PV. Twenty of the 23 neurons were examined but none projected to the thalamus. Impulse frequencies of 8 of the 11 thermoreceptive neurons examined rapidly increased with cold stimulation, then decreased and gradually increased to steady state level, and rapidly decreased with warm stimulation. Thermal receptive fields were examined for six PV thermoreceptive neurons; five had a large receptive field extending over the whole anterior tongue ipsilateral to the recording side. These findings suggest that the dorsal portion of the PV is not a thermal relay mediating thermal information from the tongue to the thalamus.

Effects of Noxious Versus Innocuous Thermal Stimulation on Lower Extremity Motor Recovery 3 Months After Stroke

ObjectiveTo examine the effects of thermal stimulation (TS) on the lower extremity (LE) movement and function in patients with stroke. DesignA double-blinded randomized controlled trial. SettingA university hospital. ParticipantsPatients (N=34) at least 3 months after stroke were randomly assigned into the experimental and the control groups. InterventionsIn addition to regular rehabilitation, the experimental group received a 30-minute noxious TS protocol (heat pain 46–47°C/cold pain 2–3°C) 3days/wk for 8 weeks, and the control group received a 30-minute innocuous TS protocol (heat 40–41°C/cold 23–24°C) 3d/wk for 8 weeks. Main Outcome MeasuresThe Low Extremity subscale of the Stroke Rehabilitation Assessment of Movement (LE-STREAM), the Mobility subscale of STREAM (Mob-STREAM), the Functional Ambulation Category (FAC), the Barthel Index (BI), the Postural Assessment Scale for Stroke Patients (PASS), and the Modified Ashworth Scale (MAS) were administered by a blinded rater at baseline, posttreatment (8wk), and follow-up (12wk). ResultsTwenty-three participants completed the study protocol and all outcome measurements. No preexisting group differences between the experimental group (n=11) and the control group (n=12) were found on demographic and clinical variables. Compared with baseline, the experimental group showed significant improvements at posttreatment and follow-up on the LE-STREAM, Mob-STREAM, FAC, and BI (P<.05) while the control group showed no significant improvements for all outcome measures. As for the between-group comparison, significant differences were seen at follow-up (12wk) on the LE-STREAM, Mob-STREAM, BI, and MAS. ConclusionsOur findings indicate that an 8-week program of noxious TS combined with a traditional stroke rehabilitation program can improve the LE-related movement and function in patients with stroke for more than 3 months.

Neurons in the trigeminal main sensory nucleus respond to innocuous thermal stimulation of the tongue in rats

Neurons in the trigeminal main sensory nucleus respond to innocuous thermal stimulation of the tongue in rats

A possible new relay for tongue thermal sense in the dorsal margin of the trigeminal principal nucleus in rats

Neurons responding to innocuous thermal stimulation of the anterior tongue were newly identified in the dorsal margin of the trigeminal principal nucleus (PV). Connections of the dorsal margin of the PV were neuroanatomically identified using wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) with electrophysiological techniques. Injection of WGA-HRP into the dorsal margin of the PV demonstrated anterograde labels distributed from the most dorsomedial portion of the posteromedial ventral nucleus (VPM) to the dorsolateral portion of the parvicellular part of the VPM and retrograde labels in the superficial layers of the caudal subnucleus of the spinal trigeminal nucleus (SpVc). Injection of WGA-HRP in the most dorsomedial portion of the VPM demonstrated retrogradely labeled cells in the dorsal margin of the PV as well as in the superficial layers of the SpVc. Tracer injection into the superficial layers of the SpVc resulted in anterograde labels in the dorsal margin of the PV as well as in the dorsomedial portion of the VPM. These findings show that neurons in the PV respond to innocuous thermal stimulation of the trigeminal field and suggest that the dorsal margin of the PV is a possible new relay for the tongue thermal sense, receiving thermal information from the superficial layers of the SpVc, the primary thermal relay for the trigeminal field, and passing the information to the thalamic relay.

Functional connectivity of the human insular cortex during noxious and innocuous thermal stimulation

The insula plays a key role in brain processing of noxious and innocuous thermal stimuli. The anterior and the posterior portions of the insular cortex are involved in different ways in nociceptive and thermoceptive processing. Therefore, their stimulus-specific functional connectivity may also differ. Here we used functional magnetic resonance imaging (fMRI) to investigate the activity and functional connectivity of insular cortex subregions during noxious and innocuous thermal stimulation. In 11 healthy subjects, psychophysically controlled noxious and innocuous warm and cold stimuli were applied to the left forearm. To differentiate between the subregions of the insular cortex involved in pain processing and those involved in temperature processing, a 2×2 factorial fMRI analysis was performed. Pain processing insular areas (main effect of pain) were detected in bilateral aINS and contralateral pINS. Temperature processing insular areas (main effect of temperature) were also found in bilateral aINS and contralateral pINS. The individual signal time courses from the pain- and temperature processing insular activation clusters were used for calculation and comparison of stimulus-specific functional connectivity of aINS and pINS by means of a correlation analysis. As expected, both aINS and pINS were functionally connected to a large brain network — which predominantly includes areas involved in nociception and thermoception: primary (S1) and secondary (S2) somatosensory cortices, cingulate gyrus, prefrontal cortex (PFC) and parietal association cortices (PA). When statistically compared, during both noxious and innocuous stimulation, aINS was more strongly connected to PFC and to ACC than was pINS; pINS meanwhile was more strongly connected to S1 and to the primary motor cortex (M1). Interestingly, S2 was more strongly connected to aINS than to pINS during painful stimulation but not during innocuous thermal stimulation. We conclude that aINS is more strongly functionally connected to areas known for affective and cognitive processing, whereas pINS is more strongly connected with areas known for sensory-discriminative processing of noxious and somatosensory stimuli.

Effect of intrathecal antidepressants on c-Fos expression induced by innocuous thermal stimulation in the spinal dorsal horn of the rats with neuropathic pain

Effect of intrathecal antidepressants on c-Fos expression induced by innocuous thermal stimulation in the spinal dorsal horn of the rats with neuropathic pain

Functional MRI of the cervical spinal cord during noxious and innocuous thermal stimulation in the α-chloralose- and halothane-anesthetized rat

Patterns of neuronal activity in the spinal cord using functional magnetic resonance imaging during noxious (48 degrees C) and innocuous (40 degrees C) thermal stimulation of the rat forepaw were examined. The patterns of functional activity elicited by thermal stimuli were compared in alpha-chloralose- and halothane-anesthetized rats. Although the locations of active pixels were similar during both types of stimulation, the mean percentage signal change was higher during noxious stimulation in both anesthetic groups. Ipsilateral dorsal horn activity was evident during both noxious and innocuous stimulation in all animals. The greatest consistency of ipsilateral dorsal horn activity occurred at the C3 to C5 spinal cord segments in all groups. Consistent contralateral dorsal horn activity appeared in segments C6 to C8 in all groups. C-fos immunohistochemical staining confirmed the presence of neural activity in the spinal cords of all animals.

Quantitative analysis of orofacial thermoreceptive neurons in the superficial medullary dorsal horn of the rat.

Surprisingly little is known concerning the central processing of innocuous thermal somatosensory information. The aim of the present study was to obtain quantitative data on the characteristics of neurons in the rat superficial medullary dorsal horn (sMDH) that responded to innocuous thermal stimulation of the rat's face and tongue. Single-unit extracellular recordings were obtained in chloralose-urethane anesthetized rats. A total of 153 thermoreceptive neurons was studied. Of these, 146 were excited by cooling and inhibited by warming and were classified as COLD cells. The remaining seven cells were excited by innocuous warming of the skin or tongue. Of 123 COLD cells tested, 33% were excited by touch and 22% by pinch stimuli delivered to the thermoreceptive field. Of the 50 COLD cells tested, 46% were excited also by noxious heating (> or = 50 degrees C for 5 s). Most (82/121) of the receptive fields were located on the upper lip, 25 on the tongue, and most of the remaining on the lower lip. Receptive fields were generally small (1-5 mm2). In some experiments, electrical stimulation in the thalamus was performed, and nine COLD cells could be activated antidromically. The responses of 38 COLD cells to incremental 5 degrees C cooling steps were examined quantitatively. Thermal stimuli were applied to facial or lingual receptive fields of sMDH neurons with a computer-controlled Peltier thermode starting from 33 degrees C, decreasing to 8 or 3 degrees C, and returning to 33 degrees C. Most COLD cells (26/38) had both static and dynamic responses; 7 had mainly dynamic and 5 mainly static responses to step decreases in temperature. Rat sMDH COLD cells could be classified into three groups depending on their stimulus-response functions. The first group (Type 1, n = 19) had a bell-shaped static stimulus response function. The second group (Type 2) had a high maintained or increasing static firing rate as the temperature decreased < 18 degrees C (n = 10). Type 3 COLD cells had mainly dynamic properties (n = 7). Many of the cells in all groups were excited by noxious mechanical stimulation. Type 2 cells differed from the other two groups in that most did not respond to noxious thermal stimuli (hot) and many responded to innocuous tactile stimuli. Neurons from each of the three groups of COLD cells could be activated antidromically from contralateral thalamus. These data suggest that there is little central processing of thermal information at the first central synapse for Type 1 neurons, however, the responses of the other two types may be due to central processing and convergence. The demonstration of rat sMDH COLD cells with distinctive stimulus-response functions to thermal shifts suggests separate functional roles of these neurons in the ascending thermal sensory pathway.

Differential distribution of fos-like immunoreactivity in the spinal trigeminal nucleus after noxious and innocuous thermal and chemical stimulation of rat cornea

Corneal afferent nerves project to two spatially distinct sites within the spinal trigeminal nucleus: the subnucleus interpolaris/caudalis transition and the subnucleus caudalis/upper cervical spinal cord transition. The role of these two regions in processing corneal input is uncertain. To determine if neurons in these regions encode different features of an applied corneal stimulus, immunoreactivity for the immediate early gene protein product, Fos, was quantified in barbiturate-anesthetized rats. Intensity was varied across thermal (thermal probe 5, 35, 42, 52 degrees C; radiant heat of approximately 45 degrees C) stimuli and compared with that seen after mustard oil (5 microliters, 20%) or mineral oil application. All stimuli increased the number of Fos-positive neurons located at the ventrolateral pole of the subnucleus interpolaris/caudalis transition compared with unstimulated controls. By contrast, only 52 degrees C thermal probe and mustard oil produced an additional peak of Fos-positive neurons within the superficial laminae at the subnucleus caudalis/cervical cord transition. Further, the magnitudes of the bimodal peaks of Fos produced by 52 degrees C thermal probe and mustard oil stimuli were different quantitatively. Mustard oil caused a greater Fos response at the subnucleus interpolaris/caudalis transition than 52 degrees C thermal probe stimulation, whereas the opposite was true at the subnucleus caudalis/cervical cord transition. Double-labeling revealed that Fos immunoreactive neurons within the spinal trigeminal nucleus were restricted to regions densely labeled for calcitonin gene-related peptide. These results indicate that select features of corneal stimuli such as modality are encoded differently by neurons in the trigeminal subnucleus interpolaris/caudalis transition compared with those located in the subnucleus caudalis/cervical cord transition. It is likely that neurons in these two brainstem regions subserve different aspects of corneal sensation.

Somatosensory, multisensory, and task-related neurons in cortical area 7b (PF) of unanesthetized monkeys.

1. The goal of this study was to quantitatively characterize the response properties of somatosensory and multisensory neurons in cortical area 7b (or PF) of monkeys that were behaviorally trained to perform an appetitive tolerance-escape task. Particular emphasis was given to characterizing nociceptive thermal responses and correlating such responses to thermal pain tolerance as measured by escape frequency. 2. A total of 244 neurons that responded to somatosensory stimulation alone or to both somatosensory and visual stimulation (multisensory) were isolated and studied in the trigeminal region of cortical area 7b. Thirty neurons responded only to visual stimulation. Thermoreceptive neurons formed approximately 13% (31 of 244) of the neurons that had somatosensory response properties. Thermal nociceptive neurons made up approximately 9% (21 of 244) of the neurons that had somatosensory response properties or approximately 68% (21 of 31) of the neurons that had thermoreceptive response properties. Thermal nociceptive neurons responded either exclusively to noxious thermal stimuli (high-threshold thermoreceptive, HTT) or differentially to nonnoxious and noxious thermal stimuli (wide-range thermoreceptive, WRT). Multimodal HTT neurons had nonnociceptive (low-threshold mechanoreceptive, LTM) and/or nociceptive (nociceptive-specific, wide-dynamic-range) mechanical receptive fields, whereas multimodal WRT neurons had only nonnociceptive (LTM) mechanical receptive fields. Thermal nonnociceptive neurons (low-threshold thermoreceptive, LTT) made up approximately 3% (8 of 244) of the neurons that had somatosensory properties or approximately 26% (8 of 31) of the neurons that were thermoreceptive. The background discharge of two thermoreceptive neurons (6%, 2 of 31) was inhibited by innocuous thermal stimulation. 3. Thermal nociceptive neurons (HTT and WRT) were functionally differentiated by statistical analyses into subpopulations that did encode (HTT-EN, WRT-EN) and did not encode (HTT-NE, WRT-NE) the magnitude of noxious thermal stimulus intensities. The mean slopes and median regression coefficients for the stimulus-response (S-R) functions of HTT-EN and WRT-EN neurons, respectively, were significantly greater than those for the S-R functions of HTT-NE and WRT-NE neurons. In contrast to HTT-NE and WRT-NE neurons, HTT-EN and WRT-EN neurons reliably encoded the magnitude of noxious thermal intensity by grading their mean discharge frequency. 4. The S-R functions of HTT-EN and WRT-EN neurons, unlike those of HTT-NE and WRT-NE neurons, closely approximated stimulus intensity-escape frequency functions.(ABSTRACT TRUNCATED AT 400 WORDS)

Fos-like immunoreactivity in the superficial medullary dorsal horn induced by noxious and innocuous thermal stimulation of facial skin in the rat

1. To examine further the ability of different classes of nociceptive and nonnociceptive primary afferent neurons to induce c-fos expression in central neurons, fos-like immunoreactivity was examined in the medullary dorsal horn (laminae I-IV) of the rat after facial application of a range of warming and cooling thermal stimuli. Urethan-anesthetized rats received 15 30-s thermal pulses (53, 50, 47, 41, 25, or 10 degrees C) applied to the vibrissal pad over a period of 30 min and were perfused 2 h after the end of stimulation. 2. Stimulation of 41 degrees C produced no significant increase in the number of fos-LI-labeled cells in lamina I or II compared with control (35 degrees C) animals. 3. Stimulation of 47 degrees C produced a significant increase in the number of fos-LI-labeled cells in both laminae I and II. Stimulation of 50 degrees C produced a significant increase in labeling, compared with that produced by 47 degrees C, which was primarily in lamina II. Stimulation of 53 degrees C produced no further increase in the number of labeled cells, compared with that produced by 50 degrees C, in lamina I or II. 4. In the cooling direction, 25 degrees C produced a significant increase in labeling above control levels in both lamina I and II, whereas 10 degrees C produced a further increase compared with 25 degrees C, which was restricted to lamina I. 5. None of the stimuli produced a significant increase in labeling in laminae III-IV. 6. The results are interpreted as providing evidence that low-threshold cold receptors, high-threshold cold receptors, and nociceptors are capable of inducing fos expression in dorsal horn neurons, whereas warm receptors are relatively ineffective. The results also provide evidence that neurons that receive input from C polymodal nociceptors are present in both laminae I and II, as are neurons that receive input from low-threshold cold receptors. Neurons that receive input from high-threshold cold receptors, but not from low-threshold cold receptors, appear to be located preferentially in lamina I. The shape of the curve relating fos-LI labeling to stimulus temperature in the warming direction is consistent with the expected pattern of recruitment of primary afferent nociceptors.

Release of sensory neuropeptides in the spinal cord: Studies with calcitonin gene-related peptide and galanin

In anaesthetized cats, antibody microprobes were used to investigate the release of immunoreactive calcitonin gene-related peptide and galanin in the lower lumbar spinal cord. In the absence of applied stimulation, a basal release of both peptides was detected at the level of the substantia gelatinosa. This release of calcitonin gene-related peptide was not altered by innocuous thermal cutaneous stimulation nor by electrical stimulation of low-threshold myelinated primary afferent fibres, but was increased by noxious thermal or noxious mechanical cutaneous stimuli and by electrical stimulation of unmyelinated primary afferents. A simultaneous release of both calcitonin gene-related peptide and substance P was detected in the substantia gelatinosa region by the use of pairs of microprobes. In contrast, none of the peripheral stimulation procedures increased intraspinal galanin release. The results suggest that the spinal transmission of nociceptive information may involve the simultaneous release and action of several neuropeptides within the superficial layers of the dorsal horn.

Cortical potentials evoked by innocuous tactile and noxious thermal stimulation in the rat: differences in localization and latency

Thermal stimulation of the rat hindleg at noxious intensities produced by laser-emitted radiant heat yielded replicable average evoked responses (AERs) in contralateral primary somatosensory cortex. In monopolar recordings, responses of opposite polarity were observed at the same depth at sites surrounding the point yielding maximum amplitude responses; potentials recorded at both central and surround sites reversed polarity in depth recordings. Compared to responses evoked by innocuous tactile stimulation, AERs to noxious thermal stimuli exhibited longer peak latencies, a more posterior localization, and a relatively higher amplitude negative component; all of these differences were statistically significant. These findings may reflect differences in central sensory mechanisms mediating the two types of stimuli and indicate the utility of the present technique for studying central mechanisms of pain perception.