Does gender affect the relation between blood pressure and pain sensitivity?

High resting blood pressure is associated with decreased pain sensitivity. This study was designed to explore this relation in young, normotensive men and women. Twenty-nine women (mean age 19.1, range 18-29) and 26 men (mean age 19.3, range 18-25) rested for 10 min while systolic, diastolic, and mean arterial blood pressures were measured. They were then asked to complete a 2-min cold pressor task. Participants were asked to fill out the short form of the McGill Pain Questionnaire immediately after the pain task. Hierarchical regression analyses were performed to predict pain sensitivity from resting blood pressure, gender, and the interaction of resting blood pressure and gender. Resting systolic blood pressure was a significant predictor of pain sensitivity. Gender and the interaction between resting blood pressure and gender were not related to pain sensitivity. This suggests that the relation between resting blood pressure and pain sensitivity may be similar in men and women, at least in response to a cold pressor challenge.     

The relationship between resting blood pressure and acute pain sensitivity: effects of chronic pain and alpha-2 adrenergic blockade

This study tested for alpha-2 adrenergic mediation of the inverse relationship between resting blood pressure and acute pain sensitivity in healthy individuals. It also replicated limited prior work suggesting this inverse blood pressure/pain association is altered in chronic pain, and provided the first test of whether chronic pain-related changes in alpha-2 adrenergic function contribute to these alterations. Resting blood pressure was assessed in 32 healthy controls and 24 chronic low back pain participants prior to receiving placebo or an intravenous alpha-2 adrenergic receptor antagonist (yohimbine hydrochloride, 0.4 mg/kg) in a randomized crossover design. Participants experienced three acute pain tasks during both sessions. A significant Systolic Blood Pressure × Participant Type × Drug interaction on finger pressure McGill Pain Questionnaire-Sensory ratings (P < .05) reflected significant hyperalgesic effects of yohimbine in chronic pain participants with lower systolic blood pressures (P < .05) but not those with higher systolic pressures, and no significant effects of yohimbine in controls regardless of blood pressure level. A Drug × Systolic Blood Pressure interaction on finger pressure visual analog scale unpleasantness indicated the inverse blood pressure/pain association was significantly stronger under yohimbine relative to placebo (P < .05). Significant Participant Type × Systolic Blood Pressure interactions (P’s < .05) were noted for finger pressure visual analog scale pain intensity and unpleasantness, ischemic pain threshold, and heat pain threshold, reflecting absence or reversal of inverse blood pressure/pain associations in chronic pain participants. Results suggest that blood pressure-related hypoalgesia can occur even when alpha-2 adrenergic systems are blocked. The possibility of upregulated alpha-2 adrenergic inhibitory function in chronic pain patients with lower blood pressure warrants further evaluation.     

Altered cardiovascular/pain regulatory relationships in chronic pain

In healthy individuals, there is an inverse relationship between resting blood pressure (BP) and pain sensitivity. This study examined possible dysregulation of this adaptive relation in chronic pain patients, and tested whether the extent of this dysregulation is a function of pain duration, Continuous resting BP_s were assessed for 5 min after a 5-min rest period in 121 chronic benign pain patients. Unlike the inverse relationship observed previously in normals, mean resting diastolic BP_s during the assessment period were correlated positively with ratings of pain severity. A Pain Duration x Systolic BP i nteraction emerged (p > .05) such that the magnitude of the BP-pain relation was greatest in patients with the longest duration of pain, r(38) = .50, p > .001. A hypothesized progressive alteration in endogenous pain regulatory systems in chronic pain patients was supported. A possible role of endogenous opioid dysfunction in accounting for these alterations is discussed. This investigation was supported by Grant BRSG S07 RR05366-28. awarded to John W. Burns by the Biomedical Research Grant Program, Division of Research Resources, National Institutes of Health. We thank Kathleen Kiselica and Ronald Pawl for allowing access to their patients at the Center for Rehabilitation at Lake Forest Hospital in Lake Forest, IL.     

Effects of Opioid Blockade with Naltrexone and Distraction on Cold and Ischemic Pain in Hypertension

Essential hypertension is characterised by reduced pain sensitivity. Hypertensive hypoalgesia has been attributed to elevated endogenous opioids and/or increased activation of descending pain modulation systems. A double-blind placebo-controlled design compared the effects of naltrexone and placebo on cold and ischemic pain in unmedicated newly-diagnosed patients with essential hypertension. Patients performed a cold pressor task while resting and while performing a distracting secondary task. They also performed a forearm ischemia task while resting. Although the cold pressor and ischemia tasks elicited significant increases in pain and blood pressure, pain ratings and pressor responses did not differ between naltrexone and placebo. Cold pain was reduced by distraction compared to rest. The finding that opioid blockade with naltrexone did not moderate the pain and pressor responses to cold and ischemia suggests that pain and associated blood pressure responses are not modulated by opioids in hypertension. The finding that the distracting secondary task successfully reduced pain ratings suggests normal supraspinal pain modulation in essential hypertension.     

Effects of Seasonal Differences in Testosterone and Cortisol Levels on Pain Responses Under Resting and Anxiety Conditions

Purpose

This study investigated whether hormones and pain perception are associated with exam anxiety, and also whether exam anxiety is affected by seasonal differences in testosterone and cortisol levels.

Materials and Methods

Forty-six healthy males were recruited from a medical college. Anxiety was induced by having participants perform the Objective Structured Clinical Examination. Pressure was applied to the participants to induce pain. Pain thresholds, pain ratings, anxiety ratings, blood pressure, heart rate, salivary testosterone and cortisol levels were measured under resting and anxiety conditions in the spring and summer. Data were collected from 46 participants during the spring (n=25) and summer (n=21).

Results

Pain thresholds and testosterone levels were significantly lower under anxiety than at rest for all participants (n=46), while cortisol levels, pain ratings, and anxiety ratings were significantly higher under anxiety than at rest. In the spring (n=25), testosterone levels were significantly higher at rest than under anxiety, while there was no difference in cortisol levels between resting and anxiety conditions. In the summer (n=21), cortisol levels were significantly higher under anxiety than at rest, while there was no difference in testosterone levels between resting and anxiety conditions. There were no significant seasonal differences in pain and anxiety ratings and pain threshold.

Conclusion

These results indicate that seasonal differences in testosterone and cortisol levels under anxiety and at rest may affect pain responses. These results also suggest that acute clinical pain may be relieved by managing anxiety that is related to a decrease of testosterone in spring and a large increase of cortisol in summer.     

Age and perceived stress independently influence daily blood pressure levels and variation among women employed in wage jobs

The purpose of this study was to examine whether age and perceived stress were independent factors affecting blood pressure variation associated with changing daily microenvironments among women employed outside the home. The subjects of this study were 91 women from the same workplace (age 33.8 ± 8.5 years; range 18.2–49.3 years) who wore an ambulatory blood pressure monitor over the course of one workday. Blood pressure averages were calculated at work (11 am to 3 pm), home (6 pm to approximately 10 pm), and during sleep (approximately 10 pm to 6 am). The stressfulness of the work and home microenvironments was rated by self‐report on a scale of 0 (low) to 10 (high). A repeated measures analysis of covariance was used to assess the cross‐classified effects of perceived stress (work stressed [work > home stress; N = 41], home stressed [home > work stress; N = 39], and equally stressed [work = home stress; N = 11]) and age group (18.0–29.9 years, N = 31; 30–39.9 years, N = 34; 40–49.9 years, N = 26) on the blood pressure averages with daily environment as a within‐subject factor and measures of body fat and menstrual phase as covariates. Work‐stressed women had higher systolic blood pressure at work, home, and during sleep than home‐stressed women (127 vs 119, P < 0.001; 124 vs 119, P < 0.05, and 111 vs 104, P < 0.005). There were similar patterns for diastolic blood pressure. Age showed a U‐shaped relationship, with women in the 30–39.9 year age range generally having lower systolic and diastolic blood pressures at work (P < 0.05), home (P < 0.10), and during sleep (P < 0.05) than younger and older age groups. The interaction between age group and perceived stress level was not significant, so that the variation in blood pressure associated with perceived stress (work stressed, home stressed, and equally stressed) was similar in each age group. Although blood pressure changes with age, environment‐related stress, particularly job‐related stress, continues to have a significant effect on daily blood pressure variation. However, data also indicate that blood pressure measured during the day may not necessarily show a linear increase with age. Am. J. Hum. Biol. 13:268–274, 2001. © 2001 Wiley‐Liss, Inc.     

Blood pressure and the perception of illusive pain

Numerous studies have documented an inverse relationship between blood pressure and sensitivity to experimental nociceptive stimulation. The present study aimed to investigate possible associations between blood pressure and the occurrence and intensity of paradoxical pain induced by the thermal grill paradigm. Thirty‐one healthy subjects were stimulated three times for 1 min with the nonnoxious temperatures of 15°C and 41°C set at the interlaced cold and warm bars of a water bath‐driven thermal grill. Blood pressure and heart rate were recorded concomitantly. On account of previous observations of an association between the sensitivity of the cardiac baroreflex and pain perception, this parameter was additionally obtained. Numerical rating scales were used to quantify subjective pain intensity and pain unpleasantness; subjects were classified as responders and nonresponders to thermal grill stimulation based on pain intensity ratings. Responders exhibited lower systolic and diastolic blood pressure than nonresponders, and inverse linear associations arose between blood pressure and pain intensity and unpleasantness. Baroreflex sensitivity was unrelated to pain ratings. The findings confirmed the hypothesis of a blood pressure dependence of paradoxical pain and support the notion that the cardiovascular and pain regulatory systems interact not only in the processing of pain elicited by noxious input, but also in nonnoxiously generated illusive pain. While this finding is not consistent with the assumption of an involvement of the baroreflex system in mediating the observed interaction, psychological traits and neurochemical factors are alternatively considered.     

Heart rate variability and pain: associations of two interrelated homeostatic processes

Between-person variability in pain sensitivity remains poorly understood. Given a conceptualization of pain as a homeostatic emotion, we hypothesized inverse associations between measures of resting heart rate variability (HRV), an index of autonomic regulation of heart rate that has been linked to emotionality, and sensitivity to subsequently administered thermal pain. Resting electrocardiography was collected, and frequency-domain measures of HRV were derived through spectral analysis. Fifty-nine right-handed participants provided ratings of pain intensity and unpleasantness following exposure to 4 degrees C thermal pain stimulation, and indicated their thresholds for barely noticeable and moderate pain during three exposures to decreasing temperature. Greater low-frequency HRV was associated with lower ratings of 4 degrees C pain unpleasantness and higher thresholds for barely noticeable and moderate pain. High-frequency HRV was unrelated to measures of pain sensitivity. Findings suggest pain sensitivity is influenced by characteristics of a central homeostatic system also involved in emotion.     

Exaggeration of blood pressure-related hypoalgesia and reduction of blood pressure with low frequency transcutaneous electrical nerve stimulation

Reduced pain perception has been observed in hypertensive individuals and normotensive individuals at risk for high blood pressure and may involve increased endogenous opioid release or receptor sensitivity. The present study examined the issue by administering two subjectively similar but physiologically different forms of the pain-reducing procedure transcutaneous electrical nerve stimulation (TENS). Men varying in resting blood pressure and parental history of hypertension participated in three testing sessions during which was presented (a) high-frequency (100 Hz) TENS; (b) low-frequency (2 Hz) TENS, the type believed to elicit endogenous opioid activity; or (c) no-TENS stimulation. Measurements of blood pressure (BP) and other physiological variables were obtained during this period. Afterwards, two pain stimuli were presented: a series of electric shocks and 5 min of arm ischemia. There was a significant negative association between pain and resting systolic blood pressure (SBP), and pain and parental history of hypertension in the no-TENS and high-frequency TENS conditions that was significantly strengthened by administration of low-frequency TENS. As well, low-frequency TENS produced a modest but significant acute reduction in SBP, especially among those with higher resting levels. These results provide further evidence that opioid mechanisms are involved in blood pressure-related hypoalgesia and blood pressure regulation.     

The daily variation in sleepiness and its relation to the preceding sleep episode—a prospective study across 42 days of normal living

Sleepiness is linked to accidents and reduced performance, and is usually attributed to short/poor prior sleep and sleepiness. However, while the link between reduced sleep and subsequent sleepiness is well established in laboratory experiments of sleep reduction, very little is known about the day‐to‐day variation of sleepiness in everyday life and its relation to the immediately preceding sleep episode. The purpose of the present study was to investigate the characteristics of this relation across 42 consecutive days. Fifty volunteers participated. Self‐reports of sleep were given in the morning and recorded with actigraphy; health was rated in the evening; and sleepiness was rated at eight points during the day (on a scale of 1–9). Results from mixed‐model regression analyses showed that, on average, total sleep time predicted sleepiness during the rest of the day across the 42 days, with sleepiness increasing with shorter preceding sleep (β = ?0.15 units h^?1, P < 0.001). Sleepiness also increased with earlier time of rising and lower‐rated sleep quality. Days off reduced sleepiness, but was accounted for by sleep. Self‐rated health improved when sleepiness was low during the same day (β = ?0.36 unit unit^?1 of rated health, P < 0.001), but the two were measured simultaneously. Napping was related to high sleepiness during the same day. Actigraphy measures of sleep duration showed similar, but somewhat weaker, effects than diary measures. It was concluded that the main determinants of daytime sleepiness in a real‐life day‐to‐day context were short sleep, poor sleep and early rising, and that days with high sleepiness ended with ratings of poorer health.     

Relationship between baroreceptor cardiac reflex sensitivity and pain experience in normotensive individuals.

In the present study, the relationship between cardiac baroreceptor function and the perception of acute pain was investigated in 60 normotensive subjects. Baroreceptor reflex sensitivity was determined using the sequence method based on continuous blood pressure recordings. A cold pressor test was used for pain induction. Visual analogue scales and a questionnaire were applied in order to quantify sensory and affective pain experience. Moderated multiple regression analysis revealed an inverse relationship between baroreceptor reflex sensitivity assessed during painful stimulation and the intensity of experienced pain. This relationship was moderated by resting blood pressure, with decreasing blood pressure being accompanied by a decrease in the magnitude of the association. Furthermore, resting blood pressure was inversely related to pain intensity. The inverse association between baroreceptor reflex sensitivity and pain experience is discussed as reflecting the well-established pain-inhibiting effect of baroreceptor activity. The finding that this relationship was less pronounced in the case of lower blood pressure suggests that baroreceptor-mediated pain attenuation is reduced in this population.     

Pain perception and cardiovascular responses in men with positive parental history for hypertension

Evidence suggests a reduced pain sensitivity in hypertensive individuals. This study sought to extend this work to normotensive individuals with hypertensive parents. Men with a positive (PH+) or negative (PH?) parental history for hypertension rated their pain every 15 s during a 90-s hand cold pressor test and for 90 s after the cold pressor test. Systolic (SBP) and diastolic (DBP) blood pressures and heart rate were measured throughout. After the cold pressor test, the men recalled their pain using the McGill Pain Questionnaire. PH+ men showed greater SBP and DBP responses to the cold pressor test. Although pain ratings during the cold pressor test did not differ between groups, posttest reported pain receded faster in the PH+ than in the PH? men. The PH+ men also reported less total pain on the McGill. These findings support the hypothesis that risk for hypertension may be associated with attenuated pain responses to nociceptive stimuli.     

Short‐term effects of repetitive arm work and dynamic exercise on glucose metabolism and insulin sensitivity

Aim: To determine whether repetitive arm work, with a large component of static muscle contraction alters glucose metabolism and insulin sensitivity. Method: Euglycemic clamps (2 h) were started in ten healthy individuals 15 min after 37 min periods of: (1) repetitive arm work in a simulated occupational setting; (2) dynamic concentric exercise on a cycle ergometer at 60% of VO_2max and (3) a resting regime as a control. During the experimental periods, blood samples were collected, blood pressure was measured repeatedly and electrocardiogram (ECG) was recorded continuously. During the clamps, euglycemia was maintained at 5 mmol l^?1 and insulin was infused at 56 mU m^?2 min^?1 for 120 min. Results: The insulin‐mediated glucose disposal rate (M‐value) for the steady‐state period (60–120 min) of the clamp, tended to be lower following arm work than for both cycling and resting regimes. When dividing the steady‐state period into 20‐min intervals, the insulin sensitivity index (ISI) was significantly lower for arm work compared with the resting control situation between 60–80 min (P = 0.04) and 80–100 min (P = 0.01), respectively. Catecholamines increased significantly for arm work and cycling compared with resting regime. Data from heart rate variability (HRV) measurements indicated significant sympathetic activation during repetitive arm work. Conclusion: The results indicate that repetitive arm work might acutely promote insulin resistance, whereas no such effect on insulin resistance was produced by dynamic concentric exercise.     

Hypervolemic hyperalgesia in healthy young adults

A cardiopulmonary baroreflex mechanism may be implicated in hypertensive hypoalgesia. Previous research in animals and humans has noted that manipulations that stimulate the vagus nerve are associated with predominantly anti-nociceptive effects. This study examined the effects of cardiopulmonary baroreceptor stimulation on venipuncture and intraveneous catherization pain during euvolemic and hypervolemic conditions while participants lay supine. In the euvolemic condition, participants maintained their normal diet whereas in the hypervolemic condition, they consumed additional water containing sodium citrate. As expected, blood volume was higher (P < .05) during the hypervolemic condition than the hypovolemic condition. Pain ratings were higher (P < .05) during hypervolemia compared to euvolemia. These findings suggest that increased cardiopulmonary baroreceptor activation during hypervolemia can be associated with increased sensitivity to noxious stimulation. In agreement with previously reported pro-nociceptive effects of vagus nerve stimulation, the current hyperalgesia finding provides further evidence that the cardiovascular system can influence the pain system.     

Deformation and pressure propagation in deep tissue during mechanical painful pressure stimulation

Manual palpation or pressure stimulation is often used for pain sensitivity assessment. The aim of the current study was to define a method for investigating the relation between pressure pain sensitivity and pressure propagation in soft or harder muscles. Three-dimensional finite-element computer-models were developed to simulate the tissue stress and strain distribution during pressure stimulation on the tibialis anterior and gastrocnemius muscles. Four cases were modelled representing females and males who were trained and untrained. The model geometry was based on MR images of the lower leg during pressure stimulation. Stress and strain were extracted from the models at pressure intensity levels equivalent to the pressure pain threshold. The principal strain peaked in the adipose tissue at 0.30 and 0.14 for stimulation on the gastrocnemius and tibialis anterior muscle, respectively. The principal strain in the muscle was higher for four models of the stimulation on the gastrocnemius muscle (0.22–0.30) compared with the four models of stimulation on the tibialis anterior muscle (0.11–0.14). Average pressure pain thresholds were significantly lower for the tibialis anterior compared with the gastrocnemius muscle (319 vs. 432 kPa) These data show different pressure propagation profiles in soft and hard muscle at the same pressure pain sensation level. This new approach is relevant as the clinical routine assesses all muscles equally. This results in a different exposure to pressure in relation to the muscle evaluated which may affect the outcome of the examination.     

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.     

Pain sensitivity in offspring of hypertensives at rest and during baroreflex stimulation

Healthy males with a parental history of hypertension (PH+) showed reduced pain sensitivity to a constrictive thigh-cuff pressure stimulus as compared to individuals without a parental history of hypertension. The protocol included eight trials in which a thigh-cuff was inflated until the subject reported the stimulus to be painful. The PH+ group exhibited significantly lower pain sensitivity as indicated by (1) higher levels of constrictive pressure when pain was first reported and (2) lower subjective pain ratings at maximum constrictive pressure. To assess the role of baroreflex stimulation on pain sensitivity in these groups, four trials were administered concurrently with external carotid pressure stimulation. There were no significant differences in pain sensitivity in each group as a function of baroreflex stimulation. The results suggest that the hypoalgesia observed in hypertensives may predate the development of sustained elevations in blood pressure.     

Cardiovascular reactivity and positive/negative affect during conversations

Systolic and diastolic blood pressures (SBP, DBP) were measured for 70 college students before, during and after informal dyadic conversations. Participants rated the positive and negative affect they experienced during conversation. SBP and DBP increased significantly from baseline to conversation. Increases in SBP and DBP were associated with more positive affect and unrelated to negative affect. Blood pressure measures taken one week later provided a more useful assessment of resting levels than measures taken before the conversation. Relationships between BP reactivity and positive affect remained significant after controlling for resting levels of BP, amount of talk during conversation, and sex of speaker in hierarchical regression. Blood pressure elevation during social interaction may be associated with involvement or enthusiasm, rather than emotional distress; this association is not simply an artifact of talkativeness. We suggest that cardiovascular reactivity in healthy young adults engaged in nonthreatening conversations may be a widespread phenomenon and not necessarily pathological.