Increased functional connectivity between limbic brain areas in healthy individuals with high versus low sensitivity to cold pain: A resting state fMRI study.

BACKGROUND: The representation of variability in sensitivity to pain by differences in neural connectivity patterns and its association with psychological factors needs further investigation. This study assessed differences in resting-state functional connectivity (rsFC) and its association to cognitive-affective aspects of pain in two groups of healthy subjects with low versus high sensitivity to pain (LSP vs. HSP). We hypothesized that HSP will show stronger connectivity in brain regions involved in the affective-motivational processing of pain and that this higher connectivity would be related to negative affective and cognitive evaluations of pain. METHODS: Forty-eight healthy subjects were allocated to two groups according to their tolerability to cold stimulation (cold pressor test, CPT, 1°C). Group LSP (N = 24) reached the cut-off time of 180±0 sec and group HSP tolerated the CPT for an average of 13±4.8 sec. Heat, cold and mechanical evoked pain were measured, as well as pain-catastrophizing (PCS), depression, anxiety and stress (DASS-21). All subjects underwent resting state fMRI. ROI-to-ROI analysis was performed. RESULTS: In comparison to the LSP, the HSP had stronger interhemispheric connectivity of the amygdala (p = 0.01) and between the amygdala and nucleus accumbens (NAc) (p = 0.01). Amygdala connectivity was associated with higher pain catastrophizing in the HSP only (p<0.01). CONCLUSIONS: These findings suggest that high sensitivity to pain may be reflected by neural circuits involved in affective and motivational aspects of pain. To what extent this connectivity within limbic brain structures relates to higher alertness and more profound withdrawal behavior to aversive events needs to be further investigated.

More Insight on the Role of Personality Traits and Sensitivity to Experimental Pain.

PURPOSE: The present study aimed to assess the influence of personality traits on the variability of sensitivity to pain in two distinct groups of healthy subjects with low versus high sensitivity to pain (LSP vs HSP, respectively). METHODS: Healthy subjects (n=156) were allocated to two groups according to their tolerability to cold stimulation (cold pressor test, CPT, 1°C). Group LSP (n=76) reached the cut-off time of 180±0 sec, and a size matched group of HSP (n=80) tolerated the CPT for an average of 10.5±3.4 sec only. Subjects from both groups completed the self-reported pain sensitivity questionnaire (PSQ), the Pain Catastrophizing Scale (PCS), and the Neuroticism Extraversion Openness - Five Factor Inventory (NEO-FFI). RESULTS: In comparison to the LSP group, HSP individuals had higher scores of PSQ (p<0.001), catastrophizing (p=0.001), and extraversion (p=0.01). By adjusting for age and gender, mediation analyses revealed that catastrophizing mediated the relationship between neuroticism and pain sensitivity, both in the allocation of subjects to a certain group of sensitivity to pain (LSP or HSP, B=0.02 95% CI: 0.006-0.040) and in the PSQ score (B=0.01 95% CI: 0.001-0.023). CONCLUSION: These results, which were demonstrated by two different prisms (CPT and PSQ), point to the potential of the five-factor inventory and pain catastrophizing scale as tools for identifying specific personality traits associated with a high sensitivity to pain.

The relationship between sensitivity to pain and conditioned pain modulation in healthy people.

BACKGROUND: The relationship between sensitivity to pain and conditioned pain modulation (CPM) - a paradigm reflecting the activity of the endogenous descending analgesic system - is still unclear. This study aimed at investigating CPM magnitude in two distinct subgroups of healthy subjects, presenting low vs. high sensitivity to pain (LSP vs. HSP, respectively), by employing two different thermal paradigms of CPM. METHOD: Ninety-five healthy subjects (out of 293 tested) were identified as LSP (n = 48) or HSP (n = 47) according to their tolerance time to noxious cold stimulation (Cold Pressor Test, 1 °C). All subjects were exposed to two different paradigms of CPM: 1) Fixed temperature 'test-pain' (TP) where phasic, fixed painful heat stimuli of 47 °C were administered before and during a prolonged 'conditioning stimulus' (cold water at 12 °C for 30 s); and 2) Individually based 'pain-60' where TP was determined as the temperature that induced pain at a magnitude of 60 on a 0-100 rating scale (with the same conditioning stimulus). RESULT: Using both thermal paradigms, LSP subjects showed decreased CPM magnitudes in comparison to HSP (p < 0.0001 in both paradigms). Within each group, no differences in the magnitudes of CPM were found between the two paradigms. CONCLUSION: These findings show that regardless of the thermal CPM paradigm employed, healthy individuals exhibiting low sensitivity to pain have a low pain inhibition profile and vice-versa. It is suggested that in healthy subjects, pain sensitivity predisposes the magnitude of CPM and not the other way around.