Affective modulation of eyeblink reactions to noxious sural nerve stimulation: A supraspinal measure of nociceptive reactivity?

Research suggests affective picture-viewing modulates subjective and physiological reactions to noxious stimulation (pain report, heart rate acceleration, skin conductance response, nociceptive flexion reflex). Because the nociceptive flexion reflex (a spinal reflex) is modulated by picture-viewing, this suggests affective processes are able to modulate afferent nociception at spinal levels. This highlights the importance of assessing nociceptive reactivity from physiological measures mediated at different levels of the neuraxis (spinal vs. supraspinal) to help elucidate the mechanisms associated with pain regulation. The present study examined whether affective pictures modulate eyeblink reactions (a supraspinal reflex) to noxious stimulation. Healthy men and women (N = 23) were recruited from the psychology subject pool to participate. Pictures (attack, loss, neutral, food, erotica) that manipulated affective valence and arousal were presented and noxious electrodermal stimulations were delivered to the sural nerve. Picture duration (500-ms vs. 6-s) was also manipulated, balanced across picture content. Results suggested affective valence and arousal contributed to the modulation of eyeblinks. Eyeblinks were larger during highly arousing unpleasant pictures (attack) than highly arousing pleasant pictures (erotica), but low arousal pictures (loss, food) did not lead to significant modulation. Affective modulation was independent of picture duration or the perceived painfulness of noxious stimulation. This study suggests eyeblink reactions can serve as a supraspinal outcome in procedures used to study affective modulation of pain and nociception.     

Affective modulation of eyeblink reactions to noxious sural nerve stimulation: a supraspinal measure of nociceptive reactivity?

Research suggests affective picture-viewing modulates subjective and physiological reactions to noxious stimulation (pain report, heart rate acceleration, skin conductance response, nociceptive flexion reflex). Because the nociceptive flexion reflex (a spinal reflex) is modulated by picture-viewing, this suggests affective processes are able to modulate afferent nociception at spinal levels. This highlights the importance of assessing nociceptive reactivity from physiological measures mediated at different levels of the neuraxis (spinal vs. supraspinal) to help elucidate the mechanisms associated with pain regulation. The present study examined whether affective pictures modulate eyeblink reactions (a supraspinal reflex) to noxious stimulation. Healthy men and women (N=23) were recruited from the psychology subject pool to participate. Pictures (attack, loss, neutral, food, erotica) that manipulated affective valence and arousal were presented and noxious electrodermal stimulations were delivered to the sural nerve. Picture duration (500-ms vs. 6-s) was also manipulated, balanced across picture content. Results suggested affective valence and arousal contributed to the modulation of eyeblinks. Eyeblinks were larger during highly arousing unpleasant pictures (attack) than highly arousing pleasant pictures (erotica), but low arousal pictures (loss, food) did not lead to significant modulation. Affective modulation was independent of picture duration or the perceived painfulness of noxious stimulation. This study suggests eyeblink reactions can serve as a supraspinal outcome in procedures used to study affective modulation of pain and nociception.     

Dorsal column stimulation: modulation of somatosensory and autonomic function

Electric stimulation of the posterior parts of the spinal cord (dorsal column stimulation), a direct clinical off-spring of the ‘gate-control theory’ presented 30 years ago, came into use as a means of relieving intractable pain only a few years later. The method was spread rapidly in the US and in Europe and is today an important adjunct in the therapy of selected pain syndromes resistant to other forms of treatment. Especially pain due to nerve injury, pain in peripheral vascular disease as well as angina pectoris are conditions which often respond to this treatment modality. Application of electric current to the dorsal columns evokes both ortho- and antidromic activity, the former being the base for the paraesthesiae experienced by the patient during stimulation. DCS seems to selectively suppress neurogenic types of pain, but the method also has a profound influence on pain in ischemia, probably via an entirely different mechanism. The somato-sensory and autonomic modulatory properties of DCS are the subject of this review, and in discussing this, we will also touch upon the question of the mechanisms underlying the beneficial effects. Furthermore, we will try to reflect the problems of generalizing observations from the laboratory, when DCS procedures are applied to subhuman subjects without concurrant disease, to the clinical setting and the suffering patient.     

Affective reactions to acoustic stimuli

Emotional reactions to naturally occurring sounds (e.g., screams, erotica, bombs, etc.) were investigated in two studies. In Experiment 1, subjects rated the pleasure and arousal elicited when listening to each of 60 sounds, followed by an incidental free recall task. The shape of the two-dimensional affective space defined by the mean ratings for each sound was similar to that previously obtained for pictures, and, like memory for pictures, free recall was highest for emotionally arousing stimuli. In Experiment 2, autonomic and facial electromyographic (EMG) activity were recorded while a new group of subjects listened to the same set of sounds; the startle reflex was measured using visual probes. Listening to unpleasant sounds resulted in larger startle reflexes, more corrugator EMG activity, and larger heart rate deceleration compared with listening to pleasant sounds. Electrodermal reactions were larger for emotionally arousing than for neutral materials. Taken together, the data suggest that acoustic cues activate the appetitive and defensive motivational circuits underlying emotional expression in ways similar to pictures.     

Affective reactions to briefly presented pictures

Affective reactions to briefly presented pictures were investigated to determine whether fleeting stimuli engage the motivational systems mediating emotional responses. Emotional and neutral pictures were presented for 500 ms; heart rate, skin conductance, corrugator EMG, and the evoked startle reflex were measured. The time course of reflex modulation was similar to that obtained with longer (6 s) presentations, suggesting that picture processing continues in the absence of a sensory stimulus. Affective reactions found with more sustained presentation were also obtained, with more corrugator EMG activity for unpleasant pictures, and greater skin conductance reactivity for emotional pictures. Heart rate modulation, however, appears to rely on the presence of a sensory stimulus. The data also suggest that brief presentations of unpleasant pictures may result in less defensive activation than sustained presentation.     

Responses of spinocervical tract neurones to noxious stimulation of the skin.

1. Activity of single spinocervical tract neurones has been recorded in the lumbar spinal cord of chloralose anaesthetized or decerebrated cats. Reversible spinalization was produced by cold block at L3. Sensitivity of these neurones to noxious stimulation was studied by heating their cutaneous receptive fields above 40-45 degrees C. 2. Most of the units were located in lamina IV of the dorsal horn and had their receptive fields in the ipsilateral foot. All but one of the studied neurones were excited by moving hairs or by gentle mechanical stimulation of the skin. 3. Eighty-four % of the units were affected by noxious stimuli and three kinds of response were obtained: (i) 61% were excited (E-cells) by noxious heat; (ii) 19% were inhibited (I-cells); and (iii) 19% gave a mixed response reversing from excitatory to inhibitory (EI-cells). 4. E-cells had axons with a wider range of conduction velocities than the rest and also received the strongest descending inhibition from supraspinal structures. 5. The recording sites of EI-cells were located in the medial third of the dorsal horn whereas E- and I-cells were distributed over the full width of the dorsal horn. 6. The possible role of the spinocervical tract in nociception is discussed.     

Cortical and autonomic responses to noxious stimulation during anesthesia in cardiac surgery patients are moderated by preanesthetic blood pressure levels

Evidence has revealed that elevated blood pressure is associated with reduced sensitivity to noxious stimulation. The current study investigated the association between resting blood pressure and nociception during anesthesia in 32 patients undergoing cardiac surgery. Pain‐related middle latency cortical somatosensory evoked potentials (MLCEPs) elicited by noxious 50 mA median nerve stimulation were used to assess intraoperative nociception and algesia. Noxious stimulation elicited MLCEPs in 18 (56%) patients. Resting blood pressure was significantly higher in patients without MLCEP than those with MLCEP. Moreover, systolic blood pressure responses to intraoperative electrical stimulation of median nerve were blunted in the group without MLCEP compared to those with MLCEP. The current findings extend the hypertensive hypoalgesia phenomenon to the operating theatre.     

Affective modulation of tactile startle

Two studies were conducted to investigate affective modulation of startle responses to unilateral tactile probes and to determine whether such modulation is lateralized. Right-handed undergraduates received airpuffs to the left or right temple while viewing pleasant, neutral, and unpleasant pictures. Side of probe presentation was varied between the two trial blocks of the experiment in Study 1 (n= 48) but varied randomly within trial blocks in Study 2 (n= 48). Primary results were consistent across studies. Replicating and extending the findings for acoustic probes, eyeblink responses to tactile probes were larger during unpleasant than during pleasant pictures. However, affective modulation of startle did not differ reliably between the two sides of probe presentation (sensory laterality) or the two sides of the response (motor lateralily) in either study or in a combined analysis.     

Affective modulation of conditioned eyeblinks

Affective states are known to modulate reflexive actions. Aversive states potentiate defensive reflexes while appetitive states diminish them. The present study examined whether the same holds for associatively learned defensive eyeblinks to mild, initially neutral auditory stimuli. First, delay eyeblink conditioning was applied to human participants while they viewed emotionally neutral images. Next, the conditioned eyeblink responses (CRs) of the participants were tested during the viewing of unpleasant, neutral, or pleasant images. The most vigorous CRs were found during the unpleasant images, although they did not differ between neutral and pleasant images. The results add to the motivational priming hypothesis by demonstrating its partial applicability to associatively learned defensive behaviour.     

Reactions by differentially raised rhesus monkeys to noxious stimulation

Adult monkeys reared in social-sensory isolation were compared with socially raised controls in 2 studies assessing aversive reactions to electric shock. In Experiment 1, the procedure involved competition between self-paced thirst and shock avoidance, presenting the monkey with a situation in which it had to absorb 2-sec of mouth-shock on a drinking tube to obtain water. When the monkey went through a response cycle by overcoming a given shock level, taking a variable number of unshocked drinks, and going 3 min without touching the drinking tube, the current was increased one step in a range from 0.1–2.5 mA. On measures of fluid intake and time per response cycle isolate monkeys did not differ from controls, suggesting that thirst motivation did not differ between groups. On shock trials isolates tolerated higher levels of shock than controls, even though they were initially more reactive to very low current levels. Isolates also showed more negative generalized effects of shock on nonshocked drinking tube contacts at a time when controls showed almost no generalized effects. In Experiment 2, neither isolates nor controls preferred to drink from a shocked over a nonshocked tube in a 2-choice free drinking situation, indicating that shock was a noxious stimulus for both groups. Thus, as in rats and dogs, stimulus deprivation during rearing produced anomalous reactions to noxious stimulation in monkeys.     

Affective modulation of inspiratory motor drive

The present study aimed to explore inspiratory motor drive as measured by inspiratory occlusion pressure (P100) during affective picture viewing. P100 is the decrease in mouth pressure that develops 100 ms after an inspiratory effort against a closed breathing circuit. The P100 is a measure of the "central respiratory drive." Seventy-eight healthy women viewed four pictures series (160 s) varying in content: neutral, positive, threat, or pain. They also rated each picture series on pleasantness and arousal. An occlusion was applied at the onset of inspiration in 33% of the breaths. The threat and the pain picture series were associated with an increased P100 and were rated as most unpleasant and highest in arousal. We conclude that inspiratory motor drive is affectively modulated and is a measure of the respiratory response to threatful stimuli.     

Clip-induced analgesia: noxious neck pinch suppresses spinal and mesencephalic neural responses to noxious peripheral stimulation

Pinch of the nape of the neck, of mice, with a serrated clip, produces immobility and lack of responsiveness to noxious stimulation. In this study we attempted to determine whether clip application produces true blockade of nociception, independent of its immobilizing effect, and examined the level of the neuroaxis at which such an effect takes place. To this end nociception was measured using indices not requiring a motor response. Neck pinch eliminated the elevation of heart rate induced by noxious pinch of the tail without affecting heart rate by itself providing evidence for its analgesic effect. Direct evidence that neck pinch suppresses the transmission of noxious information is also provided. Neck pinch inhibits neural activity evoked by noxious peripheral stimulation while exerting minimal effects on the effects of nonnoxious stimuli. Thus, sensory evoked activity in the periaqueductal gray area, elicited by noxious electrical stimulation, but not innocuous stimuli, is inhibited by neck pinch. Similarly, neck pinch inhibits the response of spinal cord neurons to noxious but not nonnoxious stimulation. It, therefore, appears that neck pinch produces true analgesia by activating supraspinal systems which in turn acts to inhibit the transmission of nociception both at spinal and supraspinal levels.     

Affective reactions to pictures of ingroup and outgroup members

A pervasive form of social categorization among humans is between us and them. In this study, we assessed emotional reactions when people viewed pictures depicting members of the same or different ethnic group. African American and European American participants viewed a series of pleasant and unpleasant pictures portraying either ingroup or outgroup members, while physiological, behavioral, and evaluative judgments were measured. Two hypotheses were assessed. The outgroup antipathy hypothesis predicts that people will respond to outgroup pictures with more negative affect than to ingroup pictures. In contrast, the ingroup empathy hypothesis predicts that people will show exaggerated (pleasant and unpleasant) affective responses to pictures of ingroup members, due to group identification or personal relevance. The data provided no support for the antipathy hypothesis, whereas facial EMG, skin conductance, rating, and viewing time data lent support to the ingroup empathy hypothesis, in which greater pleasure and displeasure were apparent when viewing ingroup pictures.     

Affective modulation of brain potentials to painful and nonpainful stimuli

In accordance with the emotional priming hypothesis, emotions seem to modulate pain perception and pain tolerance thresholds. To further evaluate this association, event-related brain potentials (ERPs) elicited by painful and nonpainful electrical stimuli during processing of positive, neutral, and negative valenced pictures were recorded from 30 healthy volunteers. Valence of pictures affected pain ratings and the N150 elicited by painful stimuli, with lowest amplitudes for positive pictures and highest amplitudes for negative pictures. The P260 elicited by painful and nonpainful stimuli was modulated by arousal with reduced amplitudes with arousing (positive or negative) compared to neutral pictures. N150 amplitudes varying with picture valence seem to reflect an affective modulation of pain perception whereas P260 amplitudes varying with picture arousal rather reflect non-pain-specific attentional processes.     

Myelinated afferent fibres responding specifically to noxious stimulation of the skin

1. The characteristics of receptors from the hairy skin of the hind limb of cat were studied by recording from single primary afferent fibres with fine micropipettes. The distinctive features of 513 fibres conducting under 51 m/sec are described.2. Seventy-four fibres conducting between 6 and 37 m/sec were classified as nociceptors because they responded only to damaging mechanical stimulation of the skin. These fibres responded maximally to pinching the skin with a serrated forceps or to cutting the skin. Noxious heat, noxious cold, acid applied to the receptive field and bradykinin injected into skin cuts did not evoke discharges from such receptors. Typically their receptive fields were 2-5 cm long by 1-2·5 cm wide and consisted of responsive spots (under 1 mm diameter) separated by unresponsive areas. There was a tendency for the most slowly conducting fibres so classified to be the least sensitive.3. Other afferent fibres had receptive fields similar to the nociceptors; however, they were excited by substantial but not noxious mechanical deformation. Their conduction velocities overlapped those of the nociceptors and extended upwards to 51 m/sec; the most rapidly conducting fibres tended to be the most sensitive to mechanical stimuli. These insensitive mechanoreceptors or moderate pressure receptors adapted more slowly than the nociceptors.4. The majority of fine myelinated axons originated from hair receptors and had conduction velocities concentrated between 14 and 22 m/sec.5. The possible relation of these observations to pain and reactions typical of pain is considered.