Louisa Edwards

Modulation of the human nociceptive flexion reflex across the cardiac cycle

Carotid baroreceptor stimulation has been shown to dampen pain. This study tested, in 40 normotensive adults, the hypothesis that pain is lower during systole when arterial baroreceptor stimulation is maximal than diastole when stimulation is minimal. The sural nerve was stimulated electrocutaneously to obtain a nociceptive flexion reflex (NFR) threshold, and then stimulation was delivered for 28 trials at 100% NFR threshold at seven intervals after the R-wave. Nociceptive responding was indexed by electromyographic (EMG) activity elicited in the biceps femoris. Significant variations in EMG activity occurred across the cardiac cycle, with less activity midcycle, indicating that the NFR response was attenuated during systole compared to diastole. Stimulation of baroreceptors by natural changes in blood pressure during the cardiac cycle dampened nociception, and accordingly, the data support the arterial baroreflex mechanism of hypertensive hypoalgesia.

The human nociceptive flexion reflex threshold is higher during systole than diastole.

A baroreflex mechanism may explain hypertensive hypoalgesia. At rest, arterial baroreceptors are stimulated during the systolic upstroke of the pressure pulse wave. This study examined the effects of naturally occurring variations in baroreceptor activity during the cardiac cycle on an objective measure of pain, the nociceptive flexion reflex (NFR). Two interleaved up-down staircase procedures determined separate NFR thresholds during systole and diastole in 36 healthy, normotensive young adults. On odd-numbered trials, the sural nerve was stimulated electrocutaneously at R + 300 ms whereas on even-numbered trials, stimulation was delivered at R + 600 ms. The NFR threshold was higher at R + 300 ms than R + 600 ms. In contrast, stimulus intensity ratings did not differ between R + 300 ms and R + 600 ms. Stimulation of baroreceptors by natural increases in blood pressure during the systolic phase of the cardiac cycle was associated with dampened nociception.

Effects of artificial and natural baroreceptor stimulation on nociceptive responding and pain

The arterial baroreflex may mediate hypertensive hypoalgesia. Carotid baroreceptors can be artificially stimulated by neck suction and inhibited by compression. Effects of brief neck suction and compression on nociceptive responding and pain were studied in 25 normotensive adults. The sural nerve was electrocutaneously stimulated at threshold intensity during systole or diastole combined with neck suction, neck compression, or no pressure. Nociceptive responding was indexed by electromyographic activity elicited in the biceps femoris. Participants rated the intensity of sural stimulation. Although artificial baroreceptor stimulation (suction) did not affect nociceptive responding, baroreceptor inhibition (compression) reduced pain ratings. In contrast, natural baroreceptor stimulation during systole reduced nociceptive responding compared to diastole, but did not affect pain ratings. The data provide partial support for baroreflex modulation of pain.

Effects of isometric exercise on pain are mediated by blood pressure

Sensitivity to pain is reduced during exercise. The underlying mechanism has yet to be established. One possibility is that a baroreceptor-related mechanism may contribute to this exercise-induced hypoalgesia phenomenon. Accordingly, this study examined whether increases in arterial blood pressure during graded isometric exercise, which activate baroreceptors in the aortic arch and carotid sinus, could account for any effects of exercise on pain in 24 normotensive young men. Electrocutaneous stimuli were delivered to the sural nerve while participants performed isometric handgrip exercise at 1%, 15%, and 25% of their maximum voluntary contraction (MVC). Participants provided a pain intensity rating immediately following the delivery of each stimulus. Nociceptive flexion reflex (NFR) responses and thresholds were also determined to provide objective physiological correlates of pain. Pain ratings were attenuated by graded isometric exercise in a linear fashion, whereas nociceptive flexion reflex responses and thresholds were unchanged by exercise. Blood pressure increased in proportion to the force of the contraction. Mediational analyses using analyses of covariance indicated that the reduction in pain with exercise was substantially accounted for by the magnitude of the blood pressure response. These findings are consistent with an arterial baroreceptor inhibition mechanism for exercise-induced hypoalgesia.

Pain-related evoked potentials are modulated across the cardiac cycle

&NA; Evidence suggests that the arterial baroreceptors modulate pain. To examine whether cortical processing of nociception is modulated by natural variations in arterial baroreceptor stimulation during the cardiac cycle, peak‐to‐peak amplitudes of the N2–P2 pain‐related potential and pain ratings were recorded in response to noxious laser stimulation at different times during the cardiac cycle in 10 healthy males. Significant variations in the N2–P2 amplitudes occurred across the cardiac cycle, with smaller amplitudes midcycle, indicating that cortical processing of nociception was attenuated during systole compared to diastole. Pain ratings did not vary across the cardiac cycle. These data support the hypothesis that arterial baroreceptors modulate the processing of nociception during each cardiac cycle.

Sensory detection thresholds are modulated across the cardiac cycle: Evidence that cutaneous sensibility is greatest for systolic stimulation

The visceral afferent feedback hypothesis proposes that sensorimotor function is impaired by cortical inhibition associated with increased baroreceptor activation. This study is the first to examine the effects of naturally occurring variations in baroreceptor activity across the cardiac cycle on cutaneous sensory detection thresholds. In each trial, an electrocutaneous stimulus was delivered to the index finger at one of three intervals (0, 300, 600 ms) after the R-wave of the electrocardiogram. Separate interleaving up-down staircases were used to determine the 50% detection threshold for each R-wave to stimulation interval. Cutaneous sensory detection thresholds were lower for stimuli presented at R+300 ms than R+0 ms or R+600 ms. The finding that cutaneous sensibility was greater when stimulated during systole than diastole may be accounted for by a modified afferent feedback hypothesis.

Alcohol consumption and cerebral blood flow among older adults

A substantial epidemiological literature now supports the existence of a J or U-shaped association between alcohol consumption and a broad range cardiovascular health outcomes including stroke. Although it is well documented that alcoholics exhibit both global and regional cerebral hypoperfusion in the sober state, little is known regarding the effects of a broader range of alcohol consumption on cerebral blood flow (CBF). The present study employed positron emission tomography with H(2)(15)O to assess quantitative global and regional CBF in 86 participants (51 men and 35 women; mean age 60.1) as a function of self-reported weekly alcohol consumption (none, <1, 1 to <7, 7 to <15, and >15 drinks per week). Analyses controlling for age, gender, and vascular health (carotid intima-media thickness) revealed that, relative to the weighted population mean, global CBF was greater in the lightest alcohol consumption group (<1 per week) and lower in the heaviest (>15 per week). Effects did not vary across regions of interest. This report is the first to describe an inverted J-shaped relationship between alcohol consumption and CBF in the absence of stroke.

Effects of naltrexone on electrocutaneous pain in patients with hypertension compared to normotensive individuals

An opioid mechanism may help explain hypertensive hypoalgesia. A double-blind placebo-controlled design compared the effects of opioid blockade (naltrexone) and placebo on electrocutaneous pain threshold, pain tolerance, and retrospective McGill Pain Questionnaire ratings in 35 unmedicated patients with essential hypertension and 28 normotensive individuals. The hypertensives experienced less pain than normotensives during the assessment of their pain tolerance; however, this manifestation of hypertensive hypoalgesia was not moderated by naltrexone. These findings fail to support the hypothesis that essential hypertension is characterised by relative opioid insensitivity.

Nociceptive flexion reflex thresholds and pain during rest and computer game play in patients with hypertension and individuals at risk for hypertension

Supraspinal pain modulation may explain hypertensive hypoalgesia. We compared nociceptive flexion reflex (NFR) thresholds and pain during rest and computer game play in hypertensives and normotensives (Experiment 1) and normotensives with and without hypertensive parents (Experiment 2). The game was selected to modulate activity in pain pathways. NFR thresholds did not differ between groups during rest or game play. Pain ratings never differed between hypertensives and normotensives, whereas individuals with hypertensive parents reported less pain during the first two NFR assessments, compared to those without. NFR thresholds and pain were reduced by game play compared to rest. The failure of game play to differentially modulate NFR thresholds or associated pain reports between groups argues against enhanced supraspinal modulation of nociception and pain in hypertensives and those at increased risk for hypertension.

Increases in Arousal Are Associated with Reductions in the Human Nociceptive Flexion Reflex Threshold and Pain Ratings

The nociceptive flexion reflex has been regarded as an objective correlate of pain perception. This study examined whether the nociceptive flexion reflex is modulated by physiological arousal in the same manner as pain. Cardiovascular activity, nociceptive flexion reflex thresholds, and pain ratings were measured in 40 healthy adults under three conditions that demanded varying degrees of physiological arousal: Rest, number repetition, and mental arithmetic. Heart rates were faster and R-wave to pulse intervals shorter during mental arithmetic than number repetition, whereas heart rates were slower and R-wave to pulse intervals longer during rest compared to number repetition. Both mental arithmetic and number repetition were associated with reduced nociceptive flexion reflex thresholds compared to rest. Although the nociceptive flexion reflex thresholds were the same during mental arithmetic and number repetition, pain ratings were lower during mental arithmetic than number repetition and rest. The resul...