Diffuse Noxious Inhibitory Controls Effect Research Articles

Conditioned pain modulation affects the N2/P2 complex but not the N1 wave: A pilot study with laser-evoked potentials.

The 'pain-inhibits-pain' effect stems from neurophysiological mechanisms involving endogenous modulatory systems termed diffuse noxious inhibitory controls (DNIC) or conditioned pain modulation (CPM). Laser-evoked potentials (LEPs) components, the N2/P2 complex, and the N1 wave, reflect the medial and lateral pain pathway, respectively: anatomically, the lateral thalamic nuclei (LT) project mainly to the somatosensory cortex (N1 generator), while the medial thalamic nuclei (MT) are bound to the limbic cortices (N2/P2 generators). We applied a CPM protocol in which the test stimulus was laser stimulation and the conditioning stimulus was a cold pressor test. LEPs recordings were obtained from 15 healthy subjects in three different conditions: baseline, during heterotopic noxious conditioning stimulation (HNCS) and post-HNCS. We observed a significant reduction in N2/P2 amplitude during HNCS and a return to pre-test amplitude post-HNCS, whereas the N1 wave remained unchanged during and post-HNCS. Our results indicate that CPM affects only the medial pain system. The spinothalamic tract (STT) transmits to both the LT and the MT, while the spinoreticulothalamic (SRT) projects only to the MT. The reduction in the amplitude of the N2/P2 complex and the absence of change in the N1 wave suggest that DNIC inhibition on the dorsal horn neurons affects only pain transmission via the SRT, while the neurons that give rise to the STT are not involved. The N1 wave can be a reliable neurophysiological parameter for assessment of STT function in clinical practice, as it does not seem to be influenced by CPM. No reports have described the effect of DNIC on lateral and medial pain pathways. We studied the N1 wave and the N2/P2 complex to detect changes during a CPM protocol. We found a reduction in the amplitude of the N2/P2 complex and no change in the N1 wave. This suggests that the DNIC inhibitory effect on dorsal horns neurons affects only pain transmission via the SRT, whereas the neurons that give rise to the STT are not involved.

Forearm heat pain does not inhibit electrically induced tibialis anterior muscle pain

Abstract Objectives Women report more musculoskeletal pain than men. A dysfunctional pain inhibitory system has been launched as a contributing factor for these gender differences. This study used a diffuse noxious inhibitory controls (DNIC) paradigm and asked the following questions: (1) is electrically induced muscle pain inhibited by a painful heat stimulus to the forearm, and (2) does women show signs of reduced inhibition compared to men?. Methods Forty healthy subjects (20 females; 18–45 years) participated in a cross-over design with painful (45–49 °C) or non-painful (35 °C) conditioning heat stimuli (in balanced order) to the contralateral forearm. The subjects received 10 painful electrical stimuli in the tibialis anterior muscle before, during and after conditioning and rated each electrical stimulus on a 0–10cm visual analogue scale (VAS). There was 30 min between experiments. All VAS scores were normalized to scores before conditioning (100%) and analyzed by RM-ANOVA. Females participated during the ovulatory phase (days 12–14). Results There was a main effect of conditioning. VAS scores during conditioning were reduced to 90 ± 24% (mean ± S.D.) with respect to before conditioning (p = 0.02). There was no difference between painful and non-painful conditioning (p = 0.31). Neither was there any difference between genders (p = 0.28); mean male VAS scores were 91 ± 21% and mean female scores were 89 ± 27% during (vs. before) conditioning. Conclusion Electrically induced muscle pain was not inhibited by a painful heat stimulus to the forearm. The reduction in muscle pain may be results of habituation. The lack of a DNIC effect may have been caused by the relatively small skin area receiving the conditioning stimulus, and excludes a conclusion on gender effects.

Gender differences in pain modulation by diffuse noxious inhibitory controls: A systematic review

Over the last decade, extensive research has demonstrated sex differences in pain perception and modulation. Several factors have been proposed to account for the differences observed between men and women, including pain modulation through diffuse noxious inhibitory controls (DNIC). Studies investigating sex differences in DNIC have shown mixed results, with some reporting decreased DNIC effect in women compared with men, while others found no difference in DNIC between the sexes. Additional studies have investigated DNIC in both sexes without focusing on sex differences. This systematic review aimed to answer the following question: “In humans of reproductive age without chronic pain, are women more likely than men to have decreased Diffuse Noxious Inhibitory Controls?” Relevant studies were identified by computerized searches of Pubmed/Medline, Embase, Biosis, Web of Science, PsycInfo and Cochrane (from January 1980 through February 2009). The search was limited to human studies with no language restriction. The initial search identified 718 titles and abstracts. Seventeen studies were included in the final stage and data regarding age and gender of participants, methodology and outcome measurements were extracted and analyzed. The majority of studies using pain report as the outcome found significantly more efficient DNIC in males than females (mean female/male ratio = 0.54). Studies evaluating pain thresholds and nociceptive flexion reflex indicated the opposite when simply averaged across studies; however, weighted analyses of threshold found more efficient DNIC in males. Gender differences in DNIC effect depend on both the experimental methodology and the modes of measurement of the effect.

Heterotopic CO2Laser Stimulation Inhibits Tooth-Related Somatosensory Evoked Potentials

The diffuse noxious inhibitory control (DNIC) effect is the neurophysiological basis for the phenomenon that heterotopic "pain inhibits pain" in remote areas of the body. The effect of DNIC is mediated by spino-bulbo-spinal loops and a final postsynaptic inhibitory mechanism. The DNIC effect depends on intensity, duration, quality, and application site of conditioning stimulation and stimulated nerve fiber-type. DNIC induced by CO(2) laser conditioning stimulation has, however, not yet been investigated, and the present study was designed to examine this. As the indicator of test stimulation, the late component of somatosensory evoked potentials (SEPs) induced by electrical tooth stimulation and pain intensity were examined under CO(2) laser conditioning stimulation. As the conditioning stimuli, CO(2) laser energy (lambda = 10.6 microm, spot size Ø = 2 mm) was applied to the dorsum of the left hand. The maximum reductions in SEP amplitude and pain intensity evaluated using a visual analog scale were 34.7% and 28.7%, respectively during CO(2) laser conditioning stimulation. No aftereffect was observed. The present study revealed that CO(2) laser radiation attenuated the late component of SEPs induced by electrical tooth stimulation, triggering the DNIC effect but with no aftereffect.

Phenylephrine Suppresses the Pain Modulation of Diffuse Noxious Inhibitory Control in Rats

Diffuse noxious inhibitory control (DNIC) is a phenomenon whereby wide dynamic range neurons are selectively and powerfully inhibited through the central nervous system by noxious stimuli heterotopically applied to a body area distant from their excitatory receptive fields. Previous work has shown that systemic administration of an alpha1-adrenoceptor agonist, phenylephrine (PE), blocked the DNIC. We hypothesized that descending inhibitory pathways mediate the DNIC mechanism and that the neural network of the DNIC loop exists in the middle brainstem, likely in a more rostral part than formerly assumed, possibly the nucleus raphe magnus (RMg). The aim of this study was to determine whether DNIC is directly modulated by PE when administered close to the RMg. The experiments were performed on anesthetized male Sprague-Dawley rats. For administration of different drugs close to the RMg, the tip of a 33-gauge cannula was placed into an area close to the RMg as determined using the atlas of Paxinos and Watson. Single square-wave electrical stimuli were applied to the digits of the left hindpaw. The C-fiber reflex response elicited by electrical stimulation within the receptive field of the ipsilateral sural nerve was recorded from the biceps femoris muscle in the absence and presence of noxious tail immersion in warm water at 50 degrees C. The DNIC effect was calculated from a recorded electromyogram as the "inhibition rate." Saline (0.05 microL) or PE (0.05 microg/0.05 microL) was microinjected close to the RMg through the cannula. The C-fiber reflex evoked by electromyographic activity was recorded the same way. The inhibition rate of the C-fiber reflex was compared before and after administration of drugs. A paired t test was used for statistical comparison between same drug administration groups, and 1-way analysis of variance and Bonferroni multiple comparison were used for statistical analysis between different drugs. At the end of all experiments, the tissue-contacting end of the cannula tip was cauterized with an electric current to localize the drug administration site. The brain was removed, sliced in coronal sections, and stained with hematoxylin and eosin. The C-fiber reflex inhibited by noxious thermal stimuli (DNIC) was significantly blocked after the injection of PE close to the RMg. Direct administration of PE close to the RMg inhibited DNIC, thereby affecting and modulating the intrinsic pain inhibition system. These findings suggest that the RMg may be involved in the regulation of DNIC.

Central Processing of Noxious Somatic Stimuli in Patients With Irritable Bowel Syndrome Compared With Healthy Controls

To compare a central analgesic mechanism known as diffuse noxious inhibitory controls (DNIC) using somatic test stimuli and somatic conditioning stimuli, (CS) in irritable bowel syndrome (IBS) patients and healthy controls. Participants were 48 premenopausal females (27 with IBS), mean age of 29 years. The phasic heat test stimulus (peak temperature, 50 degrees C) was applied to the left palm. The DNIC effect, which measured reductions in average pain ratings (APR) during counter irritation (submersion of the participant's right hand in painful 12 degrees C circulating water) compared with baseline, was compared between groups. In addition, a second, counterbalanced, CS protocol (right hand submerged in nonpainful 32 degrees C circulating water) was performed. Differences in APR between the 2 counterirritation protocols were compared between groups to control for nonspecific effects known to influence DNIC. Psychologic measures and cardiovascular reactivity were also assessed. IBS patients demonstrated smaller DNIC than controls (P=0.011, repeated measures analysis of variance), and greater state-anxiety, depression, catastrophizing, and anger-out expression (P<0.05). Group differences in DNIC were enhanced after controlling for nonspecific effects occurring during the nonpainful CS, and for psychologic measures (P=0.001, repeated measures analysis of covariance). There were no group differences in age, cardiovascular reactivity, APR, or pain ratings for the 12 degrees C CS. These data demonstrate deficient DNIC in IBS. This is the first study to adequately control for alternative explanations of pain reduction during counterirritation. Only by controlling for nonspecific effects can evidence of deficient DNIC be attributed to dysregulation in endogenous analgesic mechanisms.

An experimental model to measure excitatory and inhibitory pain mechanisms in humans

Numerous approaches have been used to induce and measure experimental pain perception with the goal of better understanding excitatory and inhibitory pain mechanisms. In this study, the objective was to develop a simple experimental design which would enable us to elicit and measure multiple nociceptive mechanisms that have been reported to play a role in the development and persistency of chronic pain, such as temporal summation (TS) and diffuse noxious inhibitory control (DNIC). Eighty-three healthy subjects (42 men, 41 women) participated in this study where we examined pain perception of two tonic heat pain stimulation (thermode) separated by a 2 minute cold pressor test (CPT) (7 °C, 10 °C or 12 °C) which allowed us to activate DNIC. The heat pain response was characterized by a peak pain during the first 30 s, which was stronger for women ( p = 0.001). We also observed a TS phenomenon during the second minute of stimulation. DNIC's analgesia was assessed by measuring the difference in pain ratings between the two thermode procedures, before and after inducing DNIC by a cold pressure test on the opposite arm. We found that the mean pain ratings and peak pain but not TS were significantly reduced by DNIC. No sex differences were observed in DNIC analgesia. Our experimental pain design allowed us to measure several excitatory and inhibitory pain mechanisms in one experimental session. We were able to separate the effect of DNIC on the peak pain and on TS. This method is simple, sensitive and can easily be used in different population of either healthy subjects or chronic pain patients.

Effects of catastrophizing on pain perception and pain modulation

The multidimensional experience of pain is thought to be partially influenced by the pain modulation system as well as by individual psychological components. Recent studies demonstrated possible common neural network mediating both domains. The present study examined the relationships between pain perception, pain modulation, and catastrophizing in healthy subjects. Forty-eight participants (29 females and 19 males) completed the pain catastrophizing scale (PCS) and underwent psychophysical tests in order to evaluate the modulation of pain, using the diffuse noxious inhibitory control (DNIC) paradigm. Contact heat pain (47.0 degrees C applied for 1 min), which was used as the "test" stimulation, was applied before and after a physical effort that induces pain (repeated squeezing of a hand grip device), which was used as a "conditioning" stimulus. Numeric pain scale intensities (NPS, 0-10) were evaluated four times during each of two separate consecutive runs of heat stimulation. Results showed a significant positive correlation of PCS with heat pain (r = 0.48, p < 0.0005) and with muscle pain (r = 0.31, p = 0.03). In addition, significant negative correlations were found between PCS and DNIC effect (r = -0.34, p = 0.02). Moreover, once catastrophizing was entered into the regression analysis, the previously significant effect of gender was no longer found. In conclusion, individuals with high catastrophizing levels demonstrated higher pain intensities and lower effects of DNIC indicating that catastrophizing might have a significant impact on pain perception via an association with pain modulation.

Diffuse noxious inhibitory controls triggered by heterotopic CO 2 laser conditioning stimulation decreased the SEP amplitudes induced by electrical tooth stimulation with different intensity at an equally inhibitory rate

The purpose of this study was to investigate (1) whether selective A δ-fiber stimulation with CO 2 laser produces a diffuse noxious inhibitory controls (DNIC) effect in the trigeminal nerve territory; and (2) whether the DNIC effect differs depending on test stimulus intensities under constant conditioning stimuli. To examine whether the CO 2 laser radiation on the dorsum of the hand selectively stimulates A δ-fibers, laser evoked potentials (LEP) were recorded. The mean peak latency of LEP was 381.4 ms. The findings revealed that the CO 2 laser selectively stimulated A δ-fibers. Electrical tooth stimuli with 3 levels of intensities (1.2, 1.4, 1.6 times the pain threshold) were applied to subjects as test stimulation in randomized order, with a CO 2 laser stimulus of 18 mJ/mm 2 applied to the dorsum of the hand for 4 min as the noxious conditioning stimulus. Somatosensory evoked potentials (SEP) induced by electrical tooth stimulation were recorded and tooth pain intensity was evaluated using a visual analogue scale (VAS). The amplitudes of the SEP late component and VAS values were significantly decreased only during the conditioning stimuli without aftereffect. The inhibitory rates of the amplitudes ranged from 31.3% to 34.6% and the VAS values from 29.0% to 31.2%. There were no significant differences in their inhibitory rates between the 3 test stimulus intensities. The result indicated that selective A δ-fiber stimulation with the CO 2 laser produces a DNIC effect in the trigeminal nerve territory and suggested that the DNIC effect does not depend on the intensity of the test stimuli.

Heterotopic ischemic pain attenuates somatosensory evoked potentials induced by electrical tooth stimulation: Diffuse noxious inhibitory controls in the trigeminal nerve territory

The purpose of this study was to determine whether the late component of somatosensory evoked potentials (SEP) induced by electrical tooth stimulation and pain intensity are inhibited by heterotopic ischemic stimulation. The tourniquet pressure with 50 mmHg greater than the individual’s systolic pressure was applied to the left upper arm for 10 min as ischemic conditioning stimulation. The late component of SEP and visual analogue scale (VAS) were recorded at 4 times and both were significantly decreased when ischemic conditioning stimulation was applied. The maximum reductions in SEP amplitude and the VAS value were 26.1% and 21.2%, respectively, during ischemic conditioning stimulation. After-effect was observed 5 min after removal of the conditioning stimulation. The present study revealed that heterotopic ischemic stimulation attenuated the late component of SEP induced by electrical tooth stimulation, triggering diffuse noxious inhibitory controls (DNIC) and after-effects in the trigeminal nerve territory. It was also suggested that the DNIC effect differs, depending on the intensity, kind, and quality of the test and conditioning stimuli.

広範囲侵害抑制性調節機構と侵害刺激強度の関係

Diffuse noxious inhibitory control (DNIC) is a phenomenon by which the effect of noxious stimuli is inhibited by heterotopic noxious stimulation. We investigated whether heterotopic conditioning stimuli could modify the second component of EMG activities of the biceps femoris reflex (C-fiber reflex) with different levels of intensity. Forty-two adult male anesthetized Wistar rats were divided into 6 groups with 6 or 8 rats in each. Three groups (8 rats in each group) were stimulated with 3 intensity levels of the electrical test stimuli, 1.2 T, 2.0 T, or 3.0 T (times the C-fiber reflex threshold), respectively. Conditioning stimuli (pinch) were delivered to the upper lip of each rat. Test stimuli were delivered to the digits of the hindpaw. Another 3 groups (6 rats in each group) as control groups were given similar test stimuli without conditioning stimuli. The inhibitory magnitudes of C-fiber reflex activities between the control and lip pinch were 215.5 +/- 105.5, 277.7 +/- 159.1, 462.3 +/- 407.9 microV x ms in group 1.2 T, 2.0 T, and 3.0 T, respectively. The inhibitory magnitudes of C-fiber reflex activities in group 3.0 T at pinch were significantly increased compared with group 1.2 T and 2.0 T. The present study demonstrated that the C-fiber reflexes were inhibited by conditioning stimuli with 3 different levels of test stimuli under sevofurane anesthesia. Though it has been considered that DNIC effect does not depend on test stimulus intensity, the present study suggested that DNIC effect might be affected by the intensity of test stimuli.

The effect of multiple stimuli on the modulation of the ‘nociceptive’ blink reflex

The ‘nociceptive’ blink reflex is a method of examining human trigeminal pain pathways. We explored temporal summation of this reflex by using a train of pulses, rather than a single pulse, and remote activation of diffuse noxious inhibitory control (DNIC), to improve reliability, flexibility and nociceptive specificity of this technique. The R2 component of the nociceptive blink reflex response (nR2) was assessed in 28 healthy volunteers using between 1 and 7 pulses per stimulus train (inter-pulse interval 5 ms). The effect of DNIC on single-, double-, and triple-pulse nR2 was investigated. Compared to single pulses, double and triple pulses increased the sensation of pain, reduced the tactile and pain thresholds, and facilitated the blink reflex responses (reduced onset latency, increased magnitude and persistence of nR2). The maximal reflex facilitation was achieved using a triple pulse. Higher pulse numbers had no additional facilitatory effect. Activation of the DNIC system using heterotopic pain suppressed the nR2 evoked by double and triple stimulation by 16 and 42%, respectively, but not the nR2 from a single pulse. Stimulation with double and triple pulses may be more suitable to study influences on nociceptive pathways than single pulses and may widen the methodological flexibility of the nociceptive blink reflex technique. This technique may be useful in studying the trigeminal nociceptive system with particular reference to primary headache disorders and their neuropharmacology.

Diffuse noxious inhibitory controls (DNIC) attenuate temporal summation of second pain in normal males but not in normal females or fibromyalgia patients

Diffuse noxious inhibitory control (DNIC) is part of a central pain modulatory system that relies on spinal and supraspinal mechanisms. Previous studies have shown that fibromyalgia (FMS) patients are lacking DNIC effects on experimental pain, compared to normal control (NC) subjects. Because DNIC has a greater effect on second pain than on first pain, we hypothesized that wind-up (WU) of second pain should be attenuated by a strong conditioning stimulus. Thus, we compared DNIC's effect on WU in three groups of subjects: 11 NC males, 22 NC females, and 11 FMS females. To separately assess the contributions of distraction related mechanisms to inhibition of second pain, we designed the experiment in such a way that directed the subjects' attention to either the test or conditioning stimulus. Repeated heat taps to the thenar surface of the right hand were used as test stimuli to generate WU of second pain. Immersion of the left hand into a hot water bath was the conditioning stimulus. As previous experiments have shown, DNIC requires a strong conditioning stimulus for pain attenuation, which may be at least partly dependent on a distraction effect. DNIC significantly inhibited thermal WU pain in normal male subjects, but adding distraction to the DNIC effect did not increase the extent of this inhibition. In contrast, neither DNIC nor DNIC plus distraction attenuated thermal WU pain in female NCs. DNIC plus distraction but not DNIC alone produced significant inhibition of thermal WU pain in female FMS patients. Our results indicate that DNIC effects on experimental WU of second pain are gender specific, with women generally lacking this pain-inhibitory mechanism.

Differential effect of painful heterotopic stimulation on capsaicin-induced pain and allodynia

Painful heterotopic stimulation (HTS) may inhibit experimental and clinical pain, an effect known as diffuse noxious inhibitory control (DNIC). This study examined the effect of painful HTS on capsaicin-induced pain intensity, brush-evoked pain intensity and area of brush-evoked pain in humans. Immersion of the foot into painful cold water significantly reduced capsaicin-induced pain intensity and brush-evoked pain intensity in the contralateral forearm, but did not change area of brush-evoked pain. The observed differential effect on the magnitude of pain and hyperalgesia on the one hand and area of hyperalgesia on the other suggests that the DNIC effect on spinal activity is selective and not general.

Diffuse noxious inhibitory control. Reappraisal by pain-related somatosensory evoked potentials following CO 2 laser stimulation

The effects of DNIC (diffuse noxious inhibitory control) in humans were evaluated by means of pain SEPs (somatosensory evoked potentials) and pain visual analogue scale (VAS) following CO2 laser stimulation applied to the left knee while conditioning stimuli (non-noxious and noxious thermal stimuli) applied to the right hand. Pain SEPs were recorded from scalp electrodes following laser stimulation applied to the left knee during various conditions as follows: (1) control (without any interference), (2) non-noxious (dipping the right hand in water at 41 degrees C for 3 min), (3) noxious (dipping the right hand in water at 46 degrees C for 3 min), and (4) after-effect (3-6 min after taking the hand from the water at 46 degrees C). The present pain SEPs findings confirmed the presence of DNIC in humans, and indicates: (1) degree of pain relief was significantly correlated with changes in pain SEPs, particularly a marked decrease in amplitude, and a decrease in VAS; (2) DNIC was more effective on the second pain than the first pain; (3) the effect of DNIC gradually increased over time, but it rapidly disappeared after the conditioning stimuli ceased; and (4) DNIC was not due merely to changes of attention. I propose that the site responsible for DNIC is the brainstem or the spinal cord rather than the cerebral hemisphere.

Diffuse noxious inhibitory control. Reappraisal by pain-related somatosensory evoked potentials following CO 2 laser stimulation

The effects of DNIC (diffuse noxious inhibitory control) in humans were evaluated by means of pain SEPs (somatosensory evoked potentials) and pain visual analogue scale (VAS) following CO 2 laser stimulation applied to the left knee while conditioning stimuli (non-noxious and noxious thermal stimuli) applied to the right hand. Pain SEPs were recorded from scalp electrodes following laser stimulation applied to the left knee during various conditions as follows: (1) control (without any interference), (2) non-noxious (dipping the right hand in water at 41°C for 3 min), (3) noxious (dipping the right hand in water at 46°C for 3 min), and (4) after-effect (3–6 min after taking the hand from the water at 46°C). The present pain SEPs findings confirmed the presence of DNIC in humans, and indicates: (1) degree of pain relief was significantly correlated with changes in pain SEPs, particularly a marked decrease in amplitude, and a decrease in VAS; (2) DNIC was more effective on the second pain than the first pain; (3) the effect of DNIC gradually increased over time, but it rapidly disappeared after the conditioning stimuli ceased; and (4) DNIC was not due merely to changes of attention. I propose that the site responsible for DNIC is the brainstem or the spinal cord rather than the cerebral hemisphere.

Chronic back pain, acute postoperative pain and the activation of diffuse noxious inhibitory controls (DNIC)

The effect of the presence of either chronic or acute clinical pain on pain threshold and on the nociceptive flexion reflex (RIII) threshold was studied. The experimental pain sensation and the flexion reflex were evoked by trains of short electrical pulses. It was hypothesized that both kinds of clinical pain would be able to induce ‘diffuse noxious inhibitory controls’ (DNIC) and thereby raise the 2 experimental thresholds. Patients with chronic low back pain, patients with postoperative pain from oral surgery, and pain-free subjects were tested in 3 conditions: during baseline, after i.v. administration of a placebo, and after i.v. administration of naloxone. In comparison with 2 pain-free control groups, the 2 pain groups had a significantly higher pain threshold in all conditions. However, the RIII threshold was not significantly elevated in chronic or acute pain patients compared to controls. Naloxone had no effect on the RIII or pain threshold in any of the groups. It is concluded that the increased pain threshold which is frequently found in chronic pain patients, and which could be confirmed in the present study, does not result from a DNIC effect. The adaptation level theory offers an alternative explanation. Also, the acute postoperative pain in this study did not seem to induce DNIC. Because other forms of acute pain have been found to be effective in activating DNIC, future research should establish which pains are and which pains are not effective.

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

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

Diffuse noxious inhibitory controls (DNIC) involve trigeminothalamic and spinothalamic neurones in the rat.

Fifty-eight lumbar dorsal horn and trigeminal nucleus caudalis neurones which could be activated by both innocuous and noxious peripheral stimuli have been recorded in the anaesthetized rat. Using transcutaneous electrical stimulation to produce A and C fibre activity in these neurones from the hindpaw or facial receptive fields the ability of a distant noxious (mechanical or thermal) stimulus applied to the nose, tail, ears and paws to inhibit the neuronal activity was demonstrated. These effects have been termed diffuse noxious inhibitory controls (DNIC). DNIC produced powerful long-lasting inhibitions on all units studied in accordance with our previous results. Approximately 40% of these convergent neurones could be antidromically activated from the contralateral ventrobasal thalamus. Similar neuronal characteristics, effects of DNIC and proportions of projection cells were found in both the dorsal horn and trigeminal complex. However, the spinothalamic tract cells conducted more rapidly than the trigeminothalamic neurones. These results indicate that DNIC can produce comparable effects on the thalamic representation of the efferent activity of these spinal cord and trigeminal neurones. The possible role of DNIC in nociception is discussed.

Pharmacological evidence for the involvement of serotonergic mechanisms in diffuse noxious inhibitory controls (DNIC)

The involvement of serotonergic mechanisms in diffuse noxious inhibitory controls (DNIC) acting on dorsal horn convergent neurones has been studied in the anaesthetized rat. 35 neurones activated by transcutaneous electrical stimulation of their hindpaw receptive fields giving clear large A-fibre and C-fibre responses were recorded. These activities were conditioned by DNIC, evoked by either noxious heat applied to the tail or noxious pinch of the nose. Cinanserin (4 mg/kg i.v.) and metergoline (5 mg/kg i.v.), serotonin (5-HT) receptor blockers, strongly reduced the inhibitory effects of DNIC whilst having no significant effect on the non-conditioned responses. 5-Hydroxytryptophan, a precursor for 5-HT synthesis, significantly potentiated the effect of DNIC. These results indicate an important role for descending serotonergic pathways in DNIC. The functional role of this system is discussed.