Activating endogenous visceral pain modulation: A comparison of heterotopic stimulation methods in healthy controls

Abstract

All sensory input underlies modulation by endogenous central nervous system pathways. Dysfunctional endogenous pain modulation has been demonstrated in central sensitization and in several pain syndromes, including Irritable Bowel Syndrome (IBS) Activation of endogenous visceral pain modulation by heterotopic stimulation was compared using different methods. Rectal electrical or distension pain alone or with simultaneous (i.e. heterotopic) noxious hand or foot cold stimulation were investigated in randomized sequence in 14 male and 1 female healthy subjects. Mean pain intensities on a visual analogue scale of 0-100 (95% CI) during tonic rectal electrical and distension stimulation alone were 64 (52-76) and 55 (39-71), respectively. Rectal distension pain decreased by 36% (18-55) with simultaneous hand and by 45% (24-66) with simultaneous foot cold pain. Rectal electrical pain decreased by 45% (29-61) during hand and by 46% (28-64) during foot cold pain. Facilitation, i.e. increased rectal pain during heterotopic stimulation was observed in only 1 of 60 stimulation runs. Potent and consistent activation of endogenous visceral pain inhibition was achieved with heterotopic cold pain limb stimulation. Somato-visceral convergence did not affect the effectiveness of induction of endogenous visceral pain inhibition in healthy subjects, as hand and foot heterotopic stimulation resulted in similar pain inhibition. Pain facilitation, as shown earlier in IBS patients, was not evident in healthy controls.

Reduction of conditioned pain modulation in humans by naltrexone: an exploratory study of the effects of pain catastrophizing

“…We have previously documented individual differences in conditioned pain modulation in which a cold water bath applied to the foot significantly diminishes pain produced by a heated probe applied to the hand (King et al, 2009; Riley et al, 2010a). Similar outcomes have been reported elsewhere (Price & McHaffie, 1988; Pud et al, 2009) with differences in the effectiveness of these pain inhibitory mechanisms as a function of age (Edwards et al, 2003; Riley et al, 2010a; Washington et al, 2000), gender (Popescu et al, 2010), and chronic pain (Heymen et al, 2010; Maixner et al, 1995; Pielsticker et al, 2005; Song et al, 2006; Staud et al, 2003; Wilder-Smith et al, 2009). Considering the fact that a number of clinical pain populations exhibit a reduced capacity to inhibit pain, understanding the mechanisms modulating pain transmission and perception could assist in the prevention and/or treatment of pain (Edwards, 2005).…”

Visceral pain perception in patients with irritable bowel syndrome and healthy volunteers is affected by the MRI scanner environment

“…This variability is unlikely to be due to poor test reproducibility, as heterotopic stimulation has been validated as a reproducible method for induction of EPM in healthy volunteers. 35,62 Our data show that trait stress, anxiety and depression do not play a major role in EPM, although state psychological factors may contribute to the variability in EPM. 61 However, recent evidence in healthy controls indicates the predominant effect of anxiety or anxiety sensitivity on pain is relayed via cortical pathways and not via those assessed by heterotopic stimulation, which include major spinal and brainstem components.…”

“…The a priori elevated psychological arousal levels may explain the lack of linear relationship between background anxiety and stress and further pain changes in the scanner. 35,[52][53][54][55] The recording of state anxiety and anxiety sensitivity measures inside and outside the scanner and personality traits for characterization of further pain endophenotypes would have yielded additional useful information, but they were not available in this study. 56 The increase seen in visceral pain inside the scanner was not reproduced for somatic pain and there also was no correlation between anxiety, stress and depression and somatic pain changes in either subject group.…”

“…Heterotopic stimulation, also described as conditioned pain modulation, is a standardized method for induction of EPM. [34][35][36] Participants were then transferred to the scanner room, and moved into the MRI scanner magnet in supine position with the head coil and restraint in situ. They were instructed that they would experience rectal, foot, and rectal with foot stimulations in random sequence, exactly as had been performed outside the scanner, after a relaxation period of 30 min.…”

The balancing act: endogenous modulation of pain in functional gastrointestinal disorders

“…This pain modulation is not sufficiently explained by distraction or attentional effects, although emotional and cognitive effects feed into the same general modulatory network 44 91 92. In healthy controls, heterotopic stimulation generally achieves a pain inhibition of 15–35%, with some racial differences between Asians, Black Africans and Caucasians 76 90 93. Over the past few years work by our group has demonstrated abnormal modulation by heterotopic stimulation in 70–85% of patients with IBS, with facilitation rather than inhibition occurring in approximately 50% and weaker than normal inhibition in the majority of the remaining patients 44 45 75.…”