Phasic Painful Stimuli Research Articles

Intense and sustained pain reduces cortical responses to auditory stimuli: Implications for the interpretation of the effects of heterotopic noxious conditioning stimulation in humans.

Phasic pain stimuli are inhibited when they are applied concomitantly with a conditioning tonic stimulus at another body location (heterotopic noxious conditioning stimulation, HNCS). While the effects of HNCS are thought to rely on a spino-bulbo-spinal mechanism in animals (termed diffuse noxious inhibitory controls, DNIC), the underlying neurophysiology in humans may involve other pathways. In this study, we investigated the role of concomitant supraspinal mechanisms during HNCS by presenting auditory stimuli during a conditioning tonic painful stimulus (the cold pressor test, CPT). Considering that auditory stimuli are not conveyed through the spinal cord, any changes in brain responses to auditory stimuli during HNCS can be ascribed entirely to supraspinal mechanisms. Electroencephalography (EEG) was recorded during HNCS, and auditory stimuli were administered in three blocks, before, during and after HNCS. Nociceptive withdrawal reflexes (NWRs) were recorded at the same time points to investigate spinal processing. Our results showed that AEPs were significantly reduced during HNCS. Moreover, the amplitude of the NWR was significantly diminished during HNCS in most participants. Given that spinal and supraspinal mechanisms operate concomitantly during HNCS, the possibility of isolating their individual contributions in humans is questionable. We conclude that the net effects of HCNS are not independent from attentional/cognitive influences.

Treating pain with pain: Supraspinal mechanisms of endogenous analgesia elicited by heterotopic noxious conditioning stimulation

While being exposed to an intensive tonic pain stimulus at one area of the body, another phasic pain stimulus applied to a remote site is perceived as less painful. The neurophysiological basis for this “pain inhibits pain” phenomenon has been presumed to be an activation of the spino-bulbo-spinal mechanism termed “diffuse noxious inhibitory controls.” However, several additional mechanisms such as an activation of the descending pain control system may contribute to this observation. Here we investigated the underlying supraspinal mechanisms of “heterotopic noxious conditioning stimulations” (HNCS), representing this specific experimental constellation. We used functional magnetic resonance imaging and behavioral recordings in combination with a modified cold-pressor task and phasic painful stimuli, and investigated the contribution of endogenous opioids to this mechanism using the opioid antagonist naloxone in a double-blind crossover design. HNCS led to marked endogenous analgesia and this effect correlated positively with the perceived intensity of the tonic painful stimulus. Furthermore, HNCS was paralleled by reduced blood oxygen level dependent (BOLD) responses in classical pain-responsive regions. Conversely, HNCS led to tonic BOLD increases in subregions of the anterior cingulate cortex. The strength of functional coupling between the subgenual anterior cingulate cortex and key structures of the descending pain control system was enhanced during HNCS, which correlated positively with the individual endogenous analgesia during HNCS. These effects were in part reversed by naloxone, speaking for the contribution of endogenous opioid neurotransmission to this mechanism. Taken together, these results demonstrate a substantial contribution of higher-order brain regions to the phenomenon of hypoalgesia during HNCS.Functional magnetic resonance imaging shows how the human brain is involved in heterotopic noxious conditioning and reveals active supraspinal pain modulatory mechanisms during dual pain stimulation.

Do Intensity Ratings and Skin Conductance Responses Reliably Discriminate Between Different Stimulus Intensities in Experimentally Induced Pain?

The present study addresses the question whether pain-intensity ratings and skin conductance responses (SCRs) are able to detect different intensities of phasic painful stimuli and to determine the reliability of this discrimination. For this purpose, 42 healthy participants of both genders were assigned to either electrical, mechanical, or laser heat-pain stimulation (each n = 14). A whole range of single brief painful stimuli were delivered on the right volar forearm of the dominant hand in a randomized order. Pain-intensity ratings and SCRs were analyzed. Using generalizability theory, individual and gender differences were the main contributors to the variability of both intensity ratings and SCRs. Most importantly, we showed that pain-intensity ratings are a reliable measure for the discrimination of different pain stimulus intensities in the applied modalities. The reliability of SCR was adequate when mechanical and heat stimuli were tested but failed for the discrimination of electrical stimuli. Further studies are needed to reveal the reason for this lack of accuracy for SCRs when applying electrical pain stimuli. Our study could help researchers to better understand the relationship between pain and activation of the sympathetic nervous system. Pain researchers are furthermore encouraged to consider individual and gender differences when measuring pain intensity and the concomitant SCRs in experimental settings.

Psychophysics of phasic and tonic heat pain stimuli by quantitative sensory testing in healthy subjects

The increased use of quantitative sensory testing in the study of pain raises the need to characterize various aspects of psychophysical response to noxious stimulation in healthy subjects. The present study aims to address several issues regarding the use of heat pain stimuli: (a) Are pain scores for short-term repeated phasic stimuli consistent? (b) Does an exposure to tonic heat pain stimulus cause sensitization and change the scores for subsequent phasic stimuli? and (c) Are pain scores for phasic and tonic heat pain correlated? To address these questions, a series of four phasic heat pain stimuli of 47 °C were given to the forearms of 70 healthy volunteers, over the course of an hour. Pain scores by Visual Analog Scale (VAS) were obtained for each stimulus. In 50 subjects, a tonic heat pain of 70 s duration at 47.5 °C was given between the first and second phasic stimuli. Pain scores were obtained at four points along this tonic stimulus. Repeated measures ANOVA and a sensitive post hoc analysis indicated that, while the pain perception was reduced on the second, nearly immediate trial, subsequent VAS scores of pain perception were not different from the first (#1: 35.2±19.2; #2: 31.4±20.2, #3: 33.0±21.6; and #4: 33.2±20.1, respectively), with strong correlation among the phasic tests. The average tonic pain score was 53.7±23.1. Administration of tonic pain stimuli did not result in different VAS scores of subsequent phasic pain stimuli, compared to those subjects who did not receive tonic pain stimuli. Tonic and phasic pain were positively correlated (e.g., r=0.45, p<0.001 for the first phasic stimuli). However, no relation was found between the level of perceived pain, either for phasic or for tonic stimuli, and presence or absence of temporal summation during the tonic pain. In conclusion: (i) phasic pain scores assessments at 30′ and 60′ after baseline is consistent; (ii) tonic heat pain, despite relatively high VAS scores, does not cause a change in the scoring of subsequent phasic stimuli; and (iii) phasic and tonic pain scores correlate with each other. Thus, the normal pattern of pain perception is stable and not altered by single tonic pain stimulation.

Behavioural and hormonal effects of restraint stress and formalin test in male and female rats

The formalin test was used to measure the analgesia induced by restraint in male and female rats. Animals were restrained for 30 min or left undisturbed in their cage and then (1) killed immediately to collect blood for hormonal determinations; or (2) subcutaneously injected with formalin in the hind paw (or sham-injected), introduced to an open field for recording of behaviour, and killed at the end of this procedure. In both experiments, corticosterone was found to be higher in females. In Experiment 1, the ability of restraint to be stressful was confirmed by the increase in corticosterone in both sexes and by the decrease of testosterone in males. In Experiment 2, restraint-treatment induced a reduction in licking and flexing that was limited to the second phase. The reduction occurred in different periods and to a different degree in the two sexes; it was greater in females. Spontaneous behaviours showed sex differences in restraint-treated but not in formalin-treated animals. The results show that the hormonal effects observed after restraint are not present after the formalin test and that the marked analgesia observed with phasic painful stimuli does not occur with a longer-lasting one such as that induced by formalin, after which only partial and short-lasting effects were observed.

Corticalization of chronic pain?

p ain, the barking watchdog of our health, is normally temporary. It immobilizes the damaged muscle or joint so that healing can occur and forces us to see the doctor. This acute and subacute pain is soon and completely forgotten once it has passed. Otherwise, as has been speculated, every family would have but one child. Acute pain normally has a reason, and is then treated by removing that cause. Similarly, we can mimic pain by inducing a cause experimentally, for example, by noxious stimulation. This way we get evidence about the pain receptors and afferents, pain pathways, its central processing, thalamic contributions, and about cortical involvement. In the same manner, mechanisms of pain relief, endogeneously through diffuse noxious inhibitory control or endorphin release, exogeneously through analgesic drugs or treatments, have well been studa destructor. Pain, formerly a symptom, becomes a disease. Physicians are normally trained to cure acute illness and are often frustrated by those patients with vague pain that refuses to go. As a consequence, the patient is despaired of seeking help in vain by the fami]ydoctor, the neurologist, the psychiatrist, the psychologist, at last by alternative medicine, and even by quackery. In parallel to the derailment of pain into chronification, the scientific attempts to explain chronic pain are poor. Physiological, anatomical, or biochemical developments involved in sustained chronic pain are broadly missing. This is already true for the peripheral end. How can a brief damage induce a permanent pain? Dissection of a nerve produces only a short barrage of impulse trains for a very short period of a~couple of minutes, not days, months, or years like in the phantom limb pain. Persistent dental pain, ied with experimental pain models. The most importoo , is not necessarily coupled to correspondingly tant pain response to these stimuli in man is, of course, the verbal report. Other pain reactions, measurable in man and in animal, are withdrawal reflexes or vegetative responses, e.g., changes in blood pressure, heart action, respiration rate, and local blood circulation. Phasic pain stimuli allow the monitoring of normal and disturbed pain pathways, by microelectroneurographic recordings or scanning through surface electrodes, especially over the scalp in the form of pain-relevant changes in the spontaneous electroencephalogram. 1 All these approaches are useful to uncover the puzzle of phasic pain. Chronic pain, however, is different. It persists, day after day and night after night, leading to the endless circle of sleeplessness, depression, agony, and social isolation. Pain, the protector of life, turns into

A Psychophysical Comparison of Sensory and Affective Responses to Four Modalities of Experimental Pain

It is generally accepted that the sensory and affective components of pain may be differentially associated with various acute and chronic diseases, and that some treatment regimens are best directed toward certain aspects of the pain experience. In addition, experimental animal models have been described that presume to assess either the sensory-discriminative aspects of phasic pain or the affective responses associated with tonic pain. The present psychophysical experiment directly compares the perceived intensity and unpleasantness of sensations evoked by four types of experimental noxious stimuli: contact heat, electric shock, ischemic exercise, and cold-pressor pain. A novel pain measurement technique is described that incorporates unbounded magnitude-estimation/category scales; this technique allows precise ratio responses, while minimizing within- and between-subject variability. We observe that, relative to the perceived intensity of the individual stimuli, subjects consistently differentiate among the degrees of unpleasantness evoked by the four stimulus modalities. Ischemic exercise and cold-pressor pain evoke higher estimates of unpleasantness, and thus may better mimic the pain of chronic disease. The relative unpleasantness produced by contact heat is significantly less than that of the other modalities tested, and therefore contact heat stimuli may be ideally suited for assessing sensory-discriminative aspects of pain perception. Possible neurophysiological mechanisms underlying the observed differences in perceived unpleasantness are discussed in relation to the growing body of literature concerning tonic and phasic pain stimuli.