Top-down attentional modulation of analgesia induced by heterotopic noxious counterstimulation

Abstract

Heterotopic noxious counterstimulation (HNCS) by the application of a sustained noxious stimulus has been shown to inhibit nociceptive processes and decrease pain induced by a competing noxious stimulus. However, it is still not clear how attentional processes contribute to these effects. The main objective of this study was to compare the analgesic effects of HNCS in 2 sessions during which top-down attention was manipulated. Acute shock pain and the nociceptive flexion reflex were evoked by transcutaneous electrical stimulations of the right sural nerve in 4 blocks (15 stimuli/block): baseline, heterotopic innocuous counterstimulation (HICS), HNCS, and recovery. Counterstimulation was applied on the left upper limb with a thermode (HICS) or a cold pack (HNCS). Attention was manipulated between sessions by instructing participants to focus their attention on shock pain or counterstimulation. Shock pain ratings decreased significantly during counterstimulation (P<.001) with stronger effects of HNCS vs HICS in both sessions (P<.01). Furthermore, shock pain inhibition during HNCS relative to baseline was stronger with attention focusing on counterstimulation compared to attention focusing on shocks (P = .015). However, the relative decrease in pain ratings during HNCS vs HICS was not significantly affected by the direction of attention (P = .7). As for spinal nociceptive processes, nociceptive flexion reflex amplitude was significantly decreased during counterstimulation (P<.001) with larger reductions during HNCS compared to HICS (P = .03). However, these effects were not altered by attention (P = .35). Together, these results demonstrate that top-down attention and HNCS produce additive analgesic effects. However, attentional modulation of HNCS analgesia seems to depend on supraspinal processes.

Chronic Back Pain Is Associated with Alterations in Dopamine Neurotransmission in the Ventral Striatum

“…Illustrated on the right are plots of average regional D2/D3R activation in the areas showing significant D2/D3R activation in the entire sample (A) and in the area that showed a significant group ϫ condition interaction (B). sensitivity and tolerance have been associated with genetic polymorphisms related to DA system function (Treister et al, 2009;Jääskeläinen et al, 2014), whereas no change was found in these measures after experimental reductions in brain DA (Becker et al, 2013;Tiemann et al, 2014). Nonetheless, specifically regarding striatal DA D2/D3R function, [ 11 C]raclopride PET studies have found significant positive correlations between baseline striatal D2/D3R BP ND and pain sensitivity in HCs (Hagelberg et al, 2002;Scott et al, 2006) and in patients with FM, who showed significant positive correlations between striatal D2/D3R BP ND and measures of both experimental pain sensitivity and widespread tenderness (Wood et al, 2007).…”

“…sensitivity and tolerance have been associated with genetic polymorphisms related to DA system function (Treister et al, 2009;Jääskeläinen et al, 2014), whereas no change was found in these measures after experimental reductions in brain DA (Becker et al, 2013;Tiemann et al, 2014). Nonetheless, specifically regarding striatal DA D2/D3R function, [ 11 C]raclopride PET studies have found significant positive correlations between baseline striatal D2/D3R BP ND and pain sensitivity in HCs (Hagelberg et al, 2002;Scott et al, 2006) and in patients with FM, who showed significant positive correlations between striatal D2/D3R BP ND and measures of both experimental pain sensitivity and widespread tenderness (Wood et al, 2007). Together, these previous studies and the present data suggest that the interindividual variability in baseline striatal D2/D3R function may be an important factor in the development and persistence of generalized hyperalgesia in chronic musculoskeletal pain, which is a frequent finding not only in FM, but also in chronic back pain (Giesecke et al, 2004;O'Neill et al, 2007).…”

“…[ 11 C]carfentanil PET data were transformed into a tracer transport measure (K 1 ratio) and a receptor-related measure (distribution volume ratio, DVR) using modified Logan graphical analysis (Logan et al, 1996). The occipital cortex, an area devoid of MORs, was used as the reference region.…”

“…PET imaging studies in healthy humans using [ 11 C]raclopride, a radioligand selective for D2Rs and D3Rs, have shown that striatal D2/D3R availability (binding potential, BP ND ) at baseline is positively correlated with pain sensitivity (Hagelberg et al, 2002), whereas activation of this neurotransmitter system, assessed as acute reductions in BP ND during painful stimulation, is associated with greater pain report in the dorsal striatum and with negative affect and fear ratings in the nucleus accumbens (Scott et al, 2006). In chronic pain patients, increases in baseline striatal D2/D3R BP ND were found in orofacial pain (Hagelberg et al, 2003a;Hagelberg et al, 2003b), whereas fibromyalgia (FM) was associated with reductions in baseline D2/D3R BP ND (Wood et al, 2007).…”

“…In chronic pain patients, increases in baseline striatal D2/D3R BP ND were found in orofacial pain (Hagelberg et al, 2003a;Hagelberg et al, 2003b), whereas fibromyalgia (FM) was associated with reductions in baseline D2/D3R BP ND (Wood et al, 2007). The study by Wood et al (2007) also found that, whereas painful stimulation led to significant activation of D2/ D3R-mediated neurotransmission in healthy controls (HCs), less activation was observed in the FM sample, suggesting a blunted response of this neurotransmitter system in FM.…”