Conditioned pain modulation is more efficient in patients with painful diabetic polyneuropathy than those with nonpainful diabetic polyneuropathy

Granovsky, Yelena; Topaz, Leah Shafran; Laycock, Helen; Zubiedat, Rabab; Crystal, Shoshana; Buxbaum, Chen; Bosak, Noam; Hadad, Rafi; Domany, Erel; Khamaisi, Mogher; Sprecher, Elliot; Bennett, David L.H.; Rice, Andrew S.C.; Yarnitsky, David

doi:10.1097/j.pain.0000000000002434

Cited by 16 publications

(15 citation statements)

References 56 publications

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“…Taken together these findings support our finding that the strongest correlation of heat-based CPM with a clinical pain measure was with the painDETECT scores (an assessment of neuropathic pain). A link between neuropathic pain and CPM particularly in heat-based paradigm but not a pressure paradigm, was also recently found in a study of CPM effects using heat and pressure test paradigms in people with painful and non-painful diabetic polyneuropathy (DPN) ( 30 ). This study reported that the inhibitory CPM evoked by heat was significantly correlated with greater neuropathic pain ( 30 ).…”

Section: Discussionmentioning

confidence: 65%

“…A link between neuropathic pain and CPM particularly in heat-based paradigm but not a pressure paradigm, was also recently found in a study of CPM effects using heat and pressure test paradigms in people with painful and non-painful diabetic polyneuropathy (DPN) ( 30 ). This study reported that the inhibitory CPM evoked by heat was significantly correlated with greater neuropathic pain ( 30 ). This suggests that in our population of people with chronic pain, the severity of their clinical pain and its interference on activities of daily living may not greatly impact their ability to exhibit an experimentally-induced CPM.…”

Section: Discussionmentioning

confidence: 65%

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The Potential Clinical Utility of Pressure-Based vs. Heat-Based Paradigms to Measure Conditioned Pain Modulation in Healthy Individuals and Those With Chronic Pain

et al. 2021

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Conditioned pain modulation (CPM) is a physiological measure thought to reflect an individual's endogenous pain modulation system. CPM varies across individuals and provides insight into chronic pain pathophysiology. There is growing evidence that CPM may help predict individual pain treatment outcome. However, paradigm variabilities and practical issues have impeded widespread clinical adoption of CPM assessment. This study aimed to compare two CPM paradigms in people with chronic pain and healthy individuals. A total of 30 individuals (12 chronic pain, 18 healthy) underwent two CPM paradigms. The heat CPM paradigm acquired pain intensity ratings evoked by a test stimulus (TS) applied before and during the conditioning stimulus (CS). The pressure CPM paradigm acquired continuous pain intensity ratings of a gradually increasing TS, before and during CS. Pain intensity was rated from 0 (no pain) to 100 (worst pain imaginable); Pain50 is the stimulus level for a response rated 50. Heat and pressure CPM were calculated as a change in TS pain intensity ratings at Pain50, where negative CPM scores indicate pain inhibition. We also determined CPM in the pressure paradigm as change in pressure pain detection threshold (PDT). We found that in healthy individuals the CPM effect was significantly more inhibitory using the pressure paradigm than the heat paradigm. The pressure CPM effect was also significantly more inhibitory when based on changes at Pain50 than at PDT. However, in individuals with chronic pain there was no significant difference in pressure CPM compared to heat or PDT CPM. There was no significant correlation between clinical pain measures (painDETECT and Brief Pain Inventory) and paradigm type (heat vs. pressure), although heat-based CPM and painDETECT scores showed a trend. Importantly, the pressure paradigm could be administered in less time than the heat paradigm. Thus, our study indicates that in healthy individuals, interpretation of CPM findings should consider potential modality-dependent effects. However, in individuals with chronic pain, either heat or pressure paradigms can similarly be used to assess CPM. Given the practical advantages of the pressure paradigm (e.g., short test time, ease of use), we propose this approach to be well-suited for clinical adoption.

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 65%

The Potential Clinical Utility of Pressure-Based vs. Heat-Based Paradigms to Measure Conditioned Pain Modulation in Healthy Individuals and Those With Chronic Pain

et al. 2021

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“… 14 The same author found more efficient CPM among patients with painful diabetic neuropathy in comparison with those patients with painless diabetic neuropathy, which might result from altered sensory messages coming from tested affected body sites. 15 Cold inhibition has been found greatest during the menstrual phases when comparing the ovulatory phase to the menstrual and luteal phases. 47 It is difficult to draw any conclusion concerning the role of hormones in CPM because another study could not determine any variation of CPM during the menstrual cycle.…”

Section: Discussionmentioning

confidence: 99%

Sex-related differences in experimental pain sensitivity in subjects with painful or painless neuropathy after surgical repair of traumatic nerve injuries

Miclescu¹,

Gkatziani²,

Granlund³

et al. 2022

PR9

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“…The conditioning stimulus in the conditioned pain modulation paradigm is often applied to the upper or lower limbs, which may confound pain‐inhibitory effects in people with enhanced or diminished sensation in the limbs due to peripheral neuropathy (Granovsky et al, 2021). The present findings suggest that temple cooling inhibits pressure pain on the hand afterwards, and thus might be an appropriate conditioning stimulus in future research examining pain inhibition in people with peripheral neuropathy.…”

Section: Discussionmentioning

confidence: 99%

Temple cooling increases parasympathetic activity and decreases pressure pain on the hand

Fairchild

et al. 2022

European Journal of Pain

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Background: Applying an ice cube to the temple (the conditioning stimulus) inhibits electrically evoked pain in the forearm. The present study aimed to determine whether temple cooling also inhibits pressure-and heat-pain test stimuli in the upper limb and, if so, to investigate the intra-session test-retest reliability of this response. Additional aims were to establish whether pain inhibition evoked by temple cooling was associated with parasympathetic activity; and to explore sex differences in response. Methods:The sample consisted of 40 healthy adults (24 females). Heart rate was recorded continuously throughout the session. An ice cube (3 × 4 cm contact area) was applied for 1 min to the temple on the dominant side. Before and immediately afterwards, the pressure pain threshold was measured from the dorsal hand and sensitivity to heat (individually adjusted at baseline to elicit moderate pain) was measured from the ventral forearm. The procedures were repeated 15 min later. Results:Temple cooling inhibited pressure pain on the hand but not heat pain on the forearm. However, test-retest reliability of pressure pain inhibition was poor.Heart rate decreased during temple cooling, consistent with a "diving" reflex. Males had stronger pressure pain inhibition, lower heart rate and higher overall autonomic activity than females. However, cardiac parasympathetic activation during temple cooling was comparable in both sexes and was unrelated to pain inhibition. Conclusions: These findings indicate that temple cooling evokes pain inhibition that is stronger in males than in females. Cardiac parasympathetic activity does not appear to mediate this response. Significance:The conditioning stimulus in the conditioned pain modulation paradigm is often applied to the upper or lower limbs. This may confound paininhibitory effects in people with peripheral neuropathy who typically have enhanced or diminished sensation in the extremities. Applying an ice cube at the temple area induces pain-inhibitory effects on the upper limb after the ice is removed. Future research examining pain modulation in people with peripheral neuropathy may consider adopting temple cooling as the conditioning stimulus.

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Conditioned pain modulation is more efficient in patients with painful diabetic polyneuropathy than those with nonpainful diabetic polyneuropathy

Abstract: Unlike other chronic pain syndromes, conditioned pain modulation is more efficient in painful than non-painful diabetic neuropathy patients, possibly due to the peripheral neuropathic sensory changes.

Cited by 16 publications

References 56 publications

The Potential Clinical Utility of Pressure-Based vs. Heat-Based Paradigms to Measure Conditioned Pain Modulation in Healthy Individuals and Those With Chronic Pain

The Potential Clinical Utility of Pressure-Based vs. Heat-Based Paradigms to Measure Conditioned Pain Modulation in Healthy Individuals and Those With Chronic Pain

Sex-related differences in experimental pain sensitivity in subjects with painful or painless neuropathy after surgical repair of traumatic nerve injuries

Temple cooling increases parasympathetic activity and decreases pressure pain on the hand

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