Sensory-discriminative Aspects Of Pain Research Articles

Influence of psychometric and sleep quality features on painful mechanical sensitivity and pain modulation in patients with temporomandibular disorders.

Assessing whether combined psychometric properties and sleep quality impact painful mechanical sensitivity and pain modulation in TMD patients. A cross-sectional study using secondary data analysis of 77 TMD patients and 101 controls. All participants completed questionnaires characterizing their psychometric profile (anxiety, depression, stress and catastrophizing) and sleep quality, alongside psychophysical tests for painful mechanical sensory (mechanical pain threshold (MPT), pressure pain threshold (PPT), and wind-up ratio (WUR)) and conditioned pain modulation (CPM). Participants were grouped into "High distress" or "Low distress" categories based on psychometric properties and sleep quality using hierarchical cluster and k-means analyses. Multiple linear regression evaluated the influence of TMD, age, and the distress cluster on MPT, WUR, PPT, and CPM in masseter and thenar muscles. Differences were statistically significant when p < 0.05. The presence of TMD was the strongest predictor of mechanical painful sensitivity in the trigeminal region (MPT[F(3,174) = 51.902;p < .001;R2 = .463]; TMD presence (β = -.682) / PPT[F(3,174) = 15.573;p < .001;R2 = .198] TMD presence (β = -.452), and extra-trigeminal (MPT[F(3,174) = 35.897;p < .001;R2 = .382] TMD (β = -.647) / CPM [F(3,174) = 4.106;p < .05;R2 = .050] TMD presence (β = .197). Furthermore, neither the high distress group nor the low distress group were able to significantly influence the variation of the values of any of the psychophysical variables evaluated (p > .05). There is not a significant influence of impairment clusters based on psychological variables and sleep quality on painful mechanical sensitivity and pain modulation, regardless of the presence of TMD. This outcome suggests that psychosocial factors and sleep quality may not play a decisive role in the sensory-discriminative aspect of pain, particularly concerning painful TMD.

Brain morphometric changes in fibromyalgia and the impact of psychometric and clinical factors: a volumetric and diffusion-tensor imaging study

BackgroundPrevious studies have repeatedly found distinct brain morphometric changes in patients with fibromyalgia (FM), mainly affecting gray and white matter abnormalities in areas related to sensory and affective pain processing. However, few studies have thus far linked different types of structural changes and not much is known about behavioral and clinical determinants that might influence the emergence and progression of such changes.MethodsWe used voxel-based morphometry (VBM) and diffusion-tensor imaging (DTI) to detect regional patterns of (micro)structural gray (GM) and white matter (WM) alterations in 23 patients with FM compared to 21 healthy controls (HC), while considering the influence of demographic, psychometric, and clinical variables (age, symptom severity, pain duration, heat pain threshold, depression scores).ResultsVBM and DTI revealed striking patterns of brain morphometric changes in FM patients. Bilateral middle temporal gyrus (MTG), parahippocampal gyrus, left dorsal anterior cingulate cortex (dACC), right putamen, right caudate nucleus, and left dorsolateral prefrontal cortex (DLPFC) showed significantly decreased GM volumes. In contrast, increased GM volume was observed in bilateral cerebellum and left thalamus. Beyond that, patients displayed microstructural changes of WM connectivity within the medial lemniscus, corpus callosum, and tracts surrounding and connecting the thalamus. Sensory-discriminative aspects of pain (pain severity, pain thresholds) primarily showed negative correlations with GM within bilateral putamen, pallidum, right midcingulate cortex (MCC), and multiple thalamic substructures, whereas the chronicity of pain was negatively correlated with GM volumes within right insular cortex and left rolandic operculum. Affective-motivational aspects of pain (depressive mood, general activity) were related to GM and FA values within bilateral putamen and thalamus.ConclusionsOur results suggest a variety of distinct structural brain changes in FM, particularly affecting areas involved in pain and emotion processing such as the thalamus, putamen, and insula.

Commentary to "Challenges and opportunities in translational pain research-An opinion paper of the working group on translational pain research of the European Pain Federation (EFIC)" by Mouraux et al.

Preclinical and clinical pain science have since long suffered from lack of joint ventures that, as securely as possible, have approached problems that are relevant for the understanding of clinical pain phenomenologies and treatment (Yezierski & Hansson, 2018), the core of translational pain medicine. The uncoupling of the two has led to loss of momentum and few novel efficacious treatment remedies where needed the most, i.e., in long term pain states. Here, the area of translational pain medicine is craving for a road map so that preclinical and clinical scientists can walk hand in hand into the future with a common agenda on how to approach the search for much needed improved treatment strategies.

Empathy for social exclusion involves the sensory-discriminative component of pain: a within-subject fMRI study

Recent research has shown that experiencing events that represent a significant threat to social bonds activates a network of brain areas associated with the sensory-discriminative aspects of pain. In the present study, we investigated whether the same brain areas are involved when witnessing social exclusion threats experienced by others. Using a within-subject design, we show that an ecologically valid experience of social exclusion recruits areas coding the somatosensory components of physical pain (posterior insular cortex and secondary somatosensory cortex). Furthermore, we show that this pattern of activation not only holds for directly experienced social pain, but also during empathy for social pain. Finally, we report that subgenual cingulate cortex is the only brain area conjointly active during empathy for physical and social pain. This supports recent theories that affective processing and homeostatic regulation are at the core of empathic responses.

NMDA-receptor antagonist and morphine decrease CRPS-pain and cerebral pain representation

A combination therapy of morphine with an NMDA-receptor antagonist might be more effective than morphine without a NMDA-receptor antagonist for the relief of neuropathic pain in patients with complex regional pain syndrome (CRPS). In order to test the efficacy of this combination therapy we performed a double-blind randomized placebo-controlled study on patients suffering from CRPS of the upper extremity. We used functional magnetic resonance imaging during movement of the affected and unaffected upper hand before and after a treatment regimen of 49 days that contrasted morphine and an NMDA-receptor antagonist with morphine and placebo. We postulated superior pain relief for the combination therapy and concomitant changes in brain areas associated with nociceptive processing. Only the combination therapy reduced pain at rest and during movement, and disability. After treatment, activation in the contralateral primary somatosensory (cS1) and anterior cingulate cortex was significantly reduced when the affected hand was moved. Pain relief during therapy was related to decreased activation in cS1 and secondary somatosensory cortex (S2). Our data suggest that the combination of morphine with an NMDA-receptor antagonist significantly affects the cerebral processing of nociceptive information in CRPS. The correlation of pain relief and decrease in cortical activity in cS1 and S2 is in accordance with the expected impact of the NMDA-receptor antagonist on cerebral pain processing with emphasis on sensory-discriminative aspects of pain.

Personality characteristics of patients with chronic low back pain

BackgroundOne of the most common causes of referral to the doctor is low back pain. Psycho_ social factors play an important role in beginning and severity and stabilizing of this chronic disease. A lot of scientist believe there is a relationship between prevalence of chronic low back pain an personality characteristic .this study was perform to find personality characteristics of patients with chronic low back pain, to find relationship between prevalence of chronic low back pain(clbp)an personality characteristic. MethodThis descriptive study was performing on 101of clbp patients who suffer from clbp were referred to neurosurgery and orthopaedic clinic. Information were collected through MMPI2 (for find personality traits) &Mc Gill pain questionnaires, Visual analogue scale (VAS) and socio_ demographic characteristic questionnaires..The Mc gill pain questionnaires investigate four aspects (sensory-discriminative aspect of pain, an affective aspect of pain, cognitive_ evaluative aspect of pain and miscellaneous aspects of pain). And statistical analyses were performing with descriptive program and SPSS version 13 software. Results101 patients enter to this study, 46 of them were men and 55 were women. And the age mean was 45/5 years old. The severity of pain in women was higher than men .There is no relation between age and personality characteristic (P>.05),but the prevalence of hysteria and hypochondriasis were high in older patient .there is a relation between sex and personality characteristic in hysteria trait(p</01). And patient with high score in hysteria and hypochondriasis trait had a intensive pain according to VAS (p</01). ConclusionAs same as another studies we found hysteria and hypochondriasis as a tow factor of traits that more higher as another traits of personality. And more psychosocial factor can effect of intensity and chronicity of pain.

Medullary dorsal horn neurons providing axons to both the parabrachial nucleus and thalamus

It has often been suggested that the trigemino- and spino-thalamic pathways are highly implicated in sensory-discriminative aspects of pain, whereas the trigemino- and spino-parabrachial pathways are strongly implicated in affective/emotional aspects of pain. On the other hand, the superficial laminae of the spinal dorsal horn, where many nociceptive neurons are distributed, have been reported to contain projection neurons innervating both the parabrachial nucleus (PBN) and thalamus by way of axon collaterals (Hylden et al., 1989). For the medullary dorsal horn (caudal subnucleus of spinal trigeminal nucleus: Vc), however, the existence of such neurons has not been reported. Thus, in the present study, we examined whether the Vc might contain projection neurons sending their axons to both the thalamus and PBN. Dual retrograde labeling with fluorescence dyes was attempted. In each rat, tetramethylrhodamine-dextran amine and Fluoro-gold were stereotaxically injected into the PBN and thalamic regions, respectively. The proportion of the dually labeled Vc cells in the total population of all labeled Vc cells was about 20%. More than 90% of the dually labeled neurons were distributed in lamina I (marginal zone), less than 10% of them were located in lamina II (substantia gelatinosa), and only a few (about 1%) were found in lamina III (magnocellular zone). The results indicate that some Vc neurons in the superficial laminae mediate nociceptive information directly to the PBN and thalamus by way of axon collaterals and that the vast majority of them project to the ipsilateral PBN and contralateral thalamus.

(660): Brain mechanisms supporting intensity discrimination and memory of pain

Sensory-discriminative aspects of pain have long been thought to be processed by contralateral structures such as lateral nuclei of the thalamus and somatosensory cortices. However, little data has directly assessed the brain mechanisms supporting intensity discrimination and memory of pain. Using a combination of both psychophysical and fMRI techniques, we identified a set of brain areas involved in intensity discrimination and intensity memory of pain. Twelve healthy subjects participated in this study.

Cortical responses to pain in healthy individuals depends on pain catastrophizing

The personal experience of pain is complex and depends on physiological and psychological factors. From this latter category, pain catastrophizing plays an important role in pain behavior and response. We aimed to determine the effect of pain catastrophizing on central nociceptive processing in healthy individuals. Functional MRI was performed during two pain intensity levels evoked by electrical median nerve stimulation in 22 healthy individuals. Pain catastrophizing scores were determined for all subjects. Pain catastrophizing was not related to activity in regions associated with sensory-discriminative aspects of pain, such as the primary or secondary somatosensory cortex. Instead, during mild pain, there was a relationship between catastrophizing and activity in cortical regions associated with affective, attention, and motor aspects of pain, including dorsolateral prefrontal, insula, rostral anterior cingulate, premotor, and parietal cortices. During more intense pain, prefrontal cortical regions implicated in the top-down modulation of pain were negatively correlated with catastrophizing. These findings can be viewed from the framework of an attention model of pain catastrophizing, whereby a cortical vigilance network is engaged during mild pain, but diminished prefrontal cortical modulation impedes disengaging from and suppressing pain during more intense pain. These findings may also implicate catastrophizing in the progression to or persistence of chronic pain.

Anterior Cingulate Cortical Neuronal Activity During Perception of Noxious Thermal Stimuli in Monkeys

It has been reported that the anterior cingulate cortex (ACC) has a variety of functions relating to pain as well as pain perception. However, the underlying mechanisms for those functions remain unclear. To elucidate the functional role of the ACC in pain perception and pain-related functions such as attention to pain and escape from pain, single neuronal activity was recorded from the ACC, and the behavioral correlates of this neuronal activity was studied. A total of 667 neurons were recorded from the ACC in awake behaving monkeys. Twenty-one had modulated activity during a heat-detection task. Eighteen of these increased their firing frequency following an increase in stimulus temperature, whereas three of them had decreased firing during heating of the face. Seventy-five percent of heat-evoked responses of heat-responsive ACC neurons were significantly depressed when monkeys detected the change in magnitude of illumination of a light presented on the front panel. The neuronal activity was significantly higher when monkeys escaped from a noxious heat stimulus than when the monkeys detected a small change in temperature (T2) above a larger initial shift (T1). No relationship between firing frequency and detection latency of the T2 stimulation was observed. These findings suggest that ACC nociceptive neurons are involved in attention to pain and escape from pain but not in the sensory discriminative aspect of pain.

Left-hemisphere dominance in early nociceptive processing in the human parasylvian cortex

Pain perception comprises sensory and emotional dimensions. While the emotional experience is thought to be represented in the right hemisphere, we here report a left-hemisphere dominance for the early sensory component of pain perception using brain electrical source analysis of laser-evoked potentials. Ten right-handed subjects underwent several series of laser radiant heat stimuli to pairs of parallel lines on the dorsum of the left or right hand. Stimulus location and intensity were randomised independently. The sensory-discriminative aspects of pain were emphasised by asking the subjects to perform either a spatial or an intensity discrimination task and were contrasted with active distraction by mental arithmetics. Pain ratings obtained after each of the laser stimulus series revealed an analgesic effect of distraction (27%, P < 0.001). Four equivalent dipole sources were active in the latency range of 100–200 ms (bilateral operculoinsular cortex, midcingulate gyrus, postcentral gyrus). The sources in the operculoinsular cortex exhibited (a) the shortest peak latency (155 ± 6 ms), (b) the most pronounced enhancement during spatial and intensity discrimination tasks compared to active distraction (43%, P < 0.001), and (c) a significantly stronger source activity in the left hemisphere independent of stimulation side (23%, P < 0.05). The distribution of these sources extended into the dorsal insula. The postcentral source had the longest peak latency (180 ± 7 ms); its source strength was task-dependent (25%, P = 0.051) but exhibited no hemisphere dominance. The midcingulate source had an intermediate peak latency (169 ± 7 ms). Its source strength was modulated by tasks, but this modulation was significant only in the latency range >200 ms (46%, P < 0.001). These findings suggest a dominant role of the left frontal operculum and adjacent dorsal insula in the early sensory-discriminative dimensions of pain processing. This region has been proposed to be the cortical projection target of nociceptive pathways from the spinal cord to the ventroposteroinferior and ventromedial (its posterior part: VMpo) thalamic nuclei.

Processing of nociceptive mechanical and thermal information in central amygdala neurons with knee-joint input.

Pain has a strong emotional dimension, and the amygdala plays a key role in emotionality. The processing of nociceptive mechanical and thermal information was studied in individual neurons of the central nucleus of the amygdala, the target of the spino-parabrachio-amygdaloid pain pathway and a major output nucleus of the amygdala. This study is the first to characterize nociceptive amygdala neurons with input from deep tissue, particularly the knee joint. In 46 anesthetized rats, extracellular single-unit recordings were made from 119 central amygdala neurons that were activated orthodromically by electrical stimulation in the lateral pontine parabrachial area and were tested for receptive fields in the knee joints. Responses to brief mechanical stimulation of joints, muscles, and skin and to cutaneous thermal stimuli were recorded. Receptive-field sizes and thresholds were mapped and stimulus-response functions constructed. Neurons in the central nucleus of the amygdala with excitatory input from the knee joint (n = 62) typically had large symmetrical receptive fields in both hindlimbs or in all four extremities and responded exclusively or preferentially to noxious mechanical stimulation of deep tissue (n = 58). Noxious mechanical stimulation of the skin excited 30 of these neurons; noxious heat activated 21 neurons. Stimulus-response data were best fitted by a sigmoid nonlinear regression model rather than by a monotonically increasing linear function. Another 15 neurons were inhibited by noxious mechanical stimulation of the knee joint and other deep tissue. Fifteen neurons had no receptive field in the knee but responded to noxious stimulation of other body areas; 27 nonresponsive neurons were not activated by natural somesthetic stimulation. Our data suggest that excitation is the predominant effect of brief painful stimulation of somatic tissue on the population of central amygdala neurons with knee joint input. Their large symmetrical receptive fields and sigmoid rather than monotonically increasing linear stimulus-response functions suggest a role of nociceptive central amygdala neurons in other than sensory-discriminative aspects of pain.

Neurophysiology and functional neuroanatomy of pain perception.

The traditional view that the cerebral cortex is not involved in pain processing has been abandoned during the past decades based on anatomic and physiologic investigations in animals, and lesion, functional neuroimaging, and neurophysiologic studies in humans. These studies have revealed an extensive central network associated with nociception that consistently includes the thalamus, the primary (SI) and secondary (SII) somatosensory cortices, the insula, and the anterior cingulate cortex (ACC). Anatomic and electrophysiologic data show that these cortical regions receive direct nociceptive thalamic input. From the results of human studies there is growing evidence that these different cortical structures contribute to different dimensions of pain experience. The SI cortex appears to be mainly involved in sensory-discriminative aspects of pain. The SII cortex seems to have an important role in recognition, learning, and memory of painful events. The insula has been proposed to be involved in autonomic reactions to noxious stimuli and in affective aspects of pain-related learning and memory. The ACC is closely related to pain unpleasantness and may subserve the integration of general affect, cognition, and response selection. The authors review the evidence on which the proposed relationship between cortical areas, pain-related neural activations, and components of pain perception is based.

To the editor

The recent article by Craig identifies the spinal trajectories of some lamina I neurons of the monkey. 1 Craig AD Spinal location of ascending lamina I axons in the macaque monkey. J Pain. 2000; 1: 33-45 Abstract Full Text Full Text PDF Scopus (22) Google Scholar Although this work clarifies to some extent the locations of these axons within the spinal cord white matter, much of Craig's discussion section is devoted to preserving the idea that lamina I and lamina V neurons have important roles in pain. Although I have no quarrel with this general view, I find Craig's representation of our work and ideas 2 Price DD Dubner R Neurons that subserve the sensory discriminative aspects of pain. Pain. 1977; 3: 307-388 Abstract Full Text PDF PubMed Scopus (303) Google Scholar on the role of lamina V wide dynamic range (WDR) neurons erroneous and consequently misleading. In the first place, citing our article as supportive of “…the view that lamina V neurons were the necessary and sufficient basis for association of the STT with pain” is inappropriate, because this view was never stated anywhere in the article. Instead, we stated that “Although some assumptions must be made about the similarity between nociceptive neurons in man and monkey, these results indicate that selective activation of dorsal horn wide dynamic range neurons is a sufficient condition to produce pain.” 2 Price DD Dubner R Neurons that subserve the sensory discriminative aspects of pain. Pain. 1977; 3: 307-388 Abstract Full Text PDF PubMed Scopus (303) Google Scholar Necessary and sufficient is very different than sufficient.

Transient inhibition of responses to thermal stimuli of spinal sensory tract neurons in monkeys during sensitization by intradermal capsaicin

A secondary zone of cutaneous hyperalgesia in humans is characterized by increased pain to mechanical stimuli. In contrast, the perception of heat stimuli delivered to a secondary zone of hyperalgesia in humans often shows a paradoxical decrease in magnitude. A number of studies have shown that the responses of spinal cord neurons to cutaneous mechanical stimuli after peripheral injury model well the mechanical hyperalgesia. However, the responses of dorsal horn neurons to thermal stimuli after peripheral injury have not been as carefully studied. The present study examined the effects of intradermal capsaicin on the responses of spinal sensory projection neurons to cutaneous mechanical and thermal stimuli. Our observations indicate that the responses of identified sensory projection neurons to heat are transiently reduced at the same time that responses of these cells to mechanical stimuli are increased. These results confirm a role for sensory projection cells in signaling the sensory discriminative aspects of pain in humans and underscore the emerging complexity of dorsal horn circuitry and sensory processing.

Pain-evoked potentials: what do they really measure?

Cerebral evoked potentials (EPs) in response to painful stimuli have been recorded since the 1970s. Based on the apparent relationship of the response amplitude to intensity of stimulation, these potentials are conventionally interpreted as reflecting the sensory-discriminative aspects of pain. As such, pain-EPs provide an objective measure for sensation of pain. An alternative interpretation regards the pain-EP as comprised of at least two overlapping components, one pain-specific, the other, a P300 wave. In the case of pain, the P300 may reflect the degree of discomfort or unpleasantness, thus reflecting the emotional-motivational aspect. To establish the nature of the pain-EP, mini doses of a benzodiazepine, counterbalanced with placebo, were given to 6 normal volunteers. Benzodiazepines decrease anxiety, and so diminish the emotional response to pain, but they have no analgesic effect. In all subjects, pain perception was unchanged, while the EP wave was almost completely obliterated. We conclude that the pain-EP reflects the emotional-motivational response to pain rather than the sensory-discriminative. Thus, it provides a useful neurophysiological tool for studying the emotions associated with pain.

Chapter 14 Involvement of the spino-parabrachio -amygdaloid and -hypothalamic pathways in the autonomic and affective emotional aspects of pain

Publisher Summary This chapter discusses various aspects of pain pathways. The pain pathways and brain structures involved in pain processing, have been clearly emphasized by the powerful modern anatomical tracing techniques, which have allowed not only a better visualization of the “classical” ascending pathways, but also revealed numerous “novel” ascending tracts that participate in pain integration. Among the so-called “pain pathways”, the spinothalamic tract seems to be highly implicated in sensory-discriminative aspects of pain. The functional roles of other ascending pathways such as the spino-cervico-thalamic tract, the postsynaptic dorsal column fibers and the various components of the spinoreticular and spino-reticulo-thalamic tracts are poorly understood. The electrophysiological properties of neurons recorded in some parts of the pathways and the connections of the three termination sites that is, the central nucleus of the amygdala, the ventromedial nucleus/retrochiasmatic area and the bed nucleus of the stria terminalis indicate that these pathways are strongly implicated in autonomic, affective-emotional and emotional-memory aspects of pain. More specifically, the large output of these nociceptive pathways toward the periaqueductal grey matter, the vagal motor, the ambiguous and the pedunculopontine tegmental nuclei emphasizes the involvment of these nociceptive pathways in the emotional motor control.

Anterograde tracing of trigeminal afferent pathways from the murine tooth pulp to cortex using herpes simplex virus type 1

Due to its predominantly nociceptive innervation, viral tracing from the tooth pulp provides a potential means for tracing central pain pathways. The neural pathways from the tooth pulp to cortex were determined using in situ hybridization to detect the anterograde transneuronal spread of herpes simplex virus type 1 strain H129 following inoculation into the murine mandibular incisor pulp. Virus first appeared in the brain at day 3 in the dorsomedial region of all three subnuclei of the spinal trigeminal nucleus and the principal sensory nucleus. By days 5-6 virus had spread to the contralateral medial nucleus of the medial geniculate complex, posterior thalamus, and ventroposteromedial thalamus. At days 7-8 virus was detected in laminae IV and Va of the primary somatosensory cortex and lamina IV of the secondary somatosensory cortex in regions previously shown to receive input from the lower jaw. Several mice also showed infection of laminae II/III of the ipsilateral dysgranular insular cortex, along with labeling for virus in the ipsilateral external lateral parabrachial nucleus, posterior thalamus, and posterior basolateral amygdala. Our results are highly consistent with previous tracing and electrophysiological studies utilizing the tooth pulp and with studies implicating the infected structures in nociception. Viral spread appeared to define two separate afferent systems with infection of structures which have been implicated in the sensory-discriminative aspects of pain, such as the ventroposteromedial thalamus and somatosensory cortex, as well as in the dysgranular insular cortex and related subcortical nuclei which may have a role in the affective-motivational aspects of pain.

Single unit activity at ventromedial medulla level in the awake, freely moving rat: effects of noxious heat and light tactile stimuli onto convergent neurons

In this study, we single recorded unit activity at the ventromedial medulla(VMM) level in the awake, freely moving rat. In agreement with previous work under the same conditions, we found a vast majority of neurons which possess heterosensory and heterosegmental inputs (‘convergent’). These units are activated either by auditory or mechanical innocuous and noxious stimuli applied all over the body surface. The activation threshold of these neurons is very low since light stimulation such as air puff produce intense bursts. In addition to this highly represented neuronal class, we also find another consistent VMM group of neurons which fire in relation to precise or generalized body movements. The main result of the present work is that, in addition to auditory and mechanical inputs, a relatively high proportion of VMM convergent neurons are activated by noxious heat pulses between 43 and 51 °C. In this range, it was possible to obtain stimulus-response functions with 2 °C steps only when a skin twitch reflex produced by the heat was present, also encoding the temperature intensity. In comparison to the VMM activations produced by an intense noxious heat pulse such as 51 °C, either auditory or controlled light touch stimuli induced a more robust response in terms of maximum frequency of discharge. Differential properties of VMM neurons in relation to innocuous and noxious information were also found using repetitive stimulation: although a strong and fast habituation of the 51 °C responses was observed, this phenomenon was not present for light touch induced activations. We propose that these differential properties might reflect separate pathways reaching the VMM, the one carrying innocuous information possibly relayed through the dorsal column nuclei. Although obtaining stimulus-response functions might implicate the VMM convergent neurons in the sensory-discriminative aspect of pain, their massive heterosensory and heterosegmental inputs favor a role in more general processes such as alertness or stress. Also, due to massive convergent properties, the involvement of this neuronal class in specific bulbospinal descending control systems of nociceptive information is questionable. Finally, our results obtained in the awake, freely moving rat strongly differ from the anesthetized preparation in that we found neither nociceptive specific units nor neurons inhibited by noxious peripheral stimulations largely described in this approach.