These findings suggest that hypoalgesia associated with elevated resting BP and BRS in healthy individuals involves both diminished central sensitization (reflected in wind-up) and enhanced descending inhibition. The presence of chronic pain significantly alters the nature of these interactions. The reversal of normal interactions between overlapping systems modulating cardiovascular systems and pain in chronic pain patients may shift the healthy buffering of BP and heart rate toward instability and eventual higher BP and cardiovascular morbidity.

While experimental baroreceptor stimulation is known to elicit hypoalgesia in healthy individuals, the impact of spontaneous baroreflex sensitivity (BRS) on acute pain responses is not known. We tested for associations between BRS and pain responses in healthy individuals, whether these associations are altered in chronic low back pain (CLBP), and the role of alpha-2 adrenergic (ADRA2) mechanisms in these effects. Twenty-five healthy controls and 21 CLBP subjects completed three acute pain tasks after receiving placebo or an intravenous ADRA2 antagonist (yohimbine hydrochloride, 0.4 mg/kg) across two sessions in counterbalanced order. Resting pre-drug spontaneous BRS was assessed using the sequence method. CLBP subjects displayed lower resting BRS(Down) than controls (p<.05). Drug x BRS(Down) interactions indicated that significant BRS-related hypoalgesia on thermal pain threshold and tolerance was eliminated with yohimbine (p's<.05). Subject Type x BRS(Up) interactions on finger pressure (MPQ-Sensory) and ischemic tasks (MPQ-Sensory, pain threshold, intra-task numeric intensity ratings) indicated that inverse BRS/pain associations in controls (p's<.05) were absent in CLBP subjects. Subject TypexDrug x BRS(Down) interactions on finger pressure MPQ-Sensory and intra-task numeric intensity ratings (p's<.05) indicated that for controls, yohimbine attenuated the significant inverse BRS/pain sensitivity associations noted under placebo. In contrast, CLBP subjects displayed a nonsignificant positive BRS/pain association under placebo, with yohimbine producing an inverse association similar to controls (significant for MPQ-Sensory). Results suggest presence of spontaneous BRS-related hypoalgesia in healthy individuals that is partially mediated by ADRA2 mechanisms, and that CLBP blunts BRS-related hypoalgesia. As a group, the CLBP subjects do not manifest baroreceptor-induced antinociception.

The anger management styles of anger-in (inhibition) and anger-out (direct expression) are positively associated with pain responsiveness. Opioid blockade studies suggest that hyperalgesic effects of trait anger-out, but not those of trait anger-in, are mediated in part by opioid analgesic system dysfunction. The current study tested the opioid dysfunction hypothesis of anger-out using an alternative index of opioid function: pain-induced changes in plasma endogenous opioids. Plasma beta-endorphin (BE) was assessed at rest and again following exposure to three laboratory acute pain tasks (finger pressure, ischemic, and thermal) in 14 healthy controls and 13 chronic low back pain (LBP) subjects. As expected, acute pain ratings correlated positively with measures of anger-in (both groups) and anger-out (LBP group; p's<.05). Greater pain-induced increases in BE were associated with significantly lower pain ratings in both groups (p's <.05). Hierarchical multiple regression indicated that greater anger-out significantly predicted smaller pain-induced BE increases (p<.05). Subject type did not moderate this association (p>.10). Anger-in did not display significant main or interaction effects on pain-induced BE changes (p's >.10). The significant association between angerout and BE release partially mediated the hyperalgesic effects of anger-out on pain unpleasantness, and was not attenuated by statistical control of general negative affect. This suggests unique associations with expressive anger regulation. Elevated trait anger-out therefore appears to be associated with opioid analgesic system dysfunction, whether it is indexed by responses to opioid blockade or by examining circulating endogenous opioid levels. Possible "state × trait" interactions on these anger-related opioid system differences are discussed.

Furlan R. Lateralization of expression of neural sympathetic activity to the vessels and effects of carotid baroreceptor stimulation. Am J Physiol Heart Circ Physiol 296: H1758 -H1765, 2009. First published April 10, 2009 doi:10.1152/ajpheart.01045.2008.-Human studies suggest that cardiovascular neural sympathetic control is predominantly modulated by the right cerebral hemisphere. It is unknown whether post-ganglionic sympathetic activity [muscle sympathetic nerve activity (MSNA)] shows any functional asymmetry. Eight right-handed volunteers (3 women and 5 men, 32 Ϯ 2 yr of age) underwent ECG, beat-by-beat blood pressure, respiratory activity, and simultaneous right and left MSNA recordings during spontaneous and controlled breathing (CB, 15 breaths/min, 0.25 Hz). Dynamic carotid baroreceptor stimulation was obtained by 0.1-Hz sinusoidal suction, from 0 to Ϫ50 mmHg, randomly applied to the right, left, and combined right and left sides of the neck during CB. Laterality was assessed by changes in the MSNA burst rate (in bursts/min, and bursts/100 beats), strength [amplitude (A) and area (AA)], and the oscillatory component at 0.1 Hz during baroreceptor stimulation. Amplitude parameters were normalized by CB burst mean amplitude and area of the same side. At rest, the right and left MSNA burst rate and total MSNA activity were similar. Conversely, the right MSNA normalized burst AN (1.36 Ϯ 0.18) and AAN (1.31 Ϯ 0.16) were larger than the left MSNA AN (1.04 Ϯ 0.09) and AAN (1.02 Ϯ 0.08). Unilateral and bilateral carotid baroreflex stimulation abolished the right prevalence of AN and AAN. In conclusion, the right lateralization of sympathetic activity to the vessels is indicated by normalized burst strength parameters of bilateral MSNA recordings at rest during spontaneous breathing. Carotid baroreceptor stimulation disrupted such expression of MSNA lateralization possibly by disturbing the synchronizing action of right cerebral hemisphere. sympathetic control of circulation; muscle sympathetic nerve activity recording; burst amplitude; area; laterality SEVERAL HUMAN STUDIES support the concept that the neural sympathetic activity regulating the cardiovascular system undergoes a predominant modulation exerted by the right cerebral hemisphere (2, 4, 10, 17-19, 33, 34). The right side of the medulla was also found to be involved in cardioacceleration in vagotomized animals (16). However, it has to be pointed out that the large majority of these investigations focused on functional modifications of the sympathetic target organs, i.e., on changes of heart rate and blood pressure and their variability, and did not focus on a direct measure of right and left efferent sympathetic activity.Two studies (27, 28) addressed the problem of the potential dissimilarity between the right and left neural efferent sympathetic activity by recording simultaneously muscle sympathetic nerve activity (MSNA) in both peroneal nerves in humans. Sundlof and Wallin (27) focused on burst rate, which was found to be similar in the right and le...

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 x Participant Type x 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 x 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 x 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.