Determinants of endogenous analgesia magnitude in a diffuse noxious inhibitory control (DNIC) paradigm: Do conditioning stimulus painfulness, gender and personality variables matter?

Faculty of Social Welfare and Health Studies, University of Haifa, Israel.
Pain (Impact Factor: 5.84). 06/2008; 136(1-2):142-9. DOI: 10.1016/j.pain.2007.06.029
Source: PubMed

ABSTRACT Descending modulation of pain can be demonstrated psychophysically by dual pain stimulation. This study evaluates in 31 healthy subjects the association between parameters of the conditioning stimulus, gender and personality, and the endogenous analgesia (EA) extent assessed by diffuse noxious inhibitory control (DNIC) paradigm. Contact heat pain was applied as the test stimulus to the non-dominant forearm, with stimulation temperature at a psychophysical intensity score of 60 on a 0-100 numerical pain scale. The conditioning stimulus was a 60s immersion of the dominant hand in cold (12, 15, 18 degrees C), hot (44 and 46.5 degrees C), or skin temperature (33 degrees C) water. The test stimulus was repeated on the non-dominant hand during the last 30s of the conditioning immersion. EA extent was calculated as the difference between pain scores of the two test stimuli. State and trait anxiety and pain catastrophizing scores were assessed prior to stimulation. EA was induced only for the pain-generating conditioning stimuli at 46.5 degrees C (p=0.011) and 12 degrees C (p=0.003). EA was independent of conditioning pain modality, or personality, but a significant gender effect was found, with greater EA response in males. Importantly, pain scores of the conditioning stimuli were not correlated with EA extent. The latter is based on both our study population, and on additional 82 patients, who participated in another study, in which EA was induced by immersion at 46.5 degrees C. DNIC testing, thus, seems to be relatively independent of the stimulation conditions, making it an easy to apply tool, suitable for wide range applications in pain psychophysics.

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Available from: Michal Granot, Mar 04, 2015
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    • "conditioning stimulus seems to be more critical (Lautenbacher et al. 2002; Granot et al. 2008). Accordingly, intense and summating conditioning stimuli such as hand immersion in hot or cold water have appeared to be very effective (Lewis et al. 2012). "
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    ABSTRACT: Abstract Background: Chemo-somatosensory evoked potentials (CSSEPs) elicited by chemical stimulation (CO2 gas) of the nasal mucosa have been shown to be sensitive enough to pick up even weak analgesic effects. With the present study we wanted to investigate whether CSSEPs are also a sensitive tool to capture endogenous pain inhibitory mechanisms elicited by conditioned pain modulation (CPM; where a first conditioning stimulus reduces the sensitivity for a second test stimulus) with a conditioning stimulus of rather low noxious load. Methods: Seventeen healthy participants were tested for CPM effects (conditioning stimulus: tonic heat pain with intensities around the pain threshold induced via a thermode; test stimulus: chemonasal stimulation (73% and 78% CO2)) on CSSEPs and on self-report ratings. Results: We found significant CPM effects in the CSSEPS, with reduced amplitudes and prolonged latencies at several electroencephalogram (EEG) recording positions when using the lower CO2 concentration (73% CO2). In contrast to the visible inhibitory effects on the CSSEPs, subjective ratings of the test stimulus did not reflect CPM action. Discussion: The experimental pain model using CO2 stimuli to elicit CSSEPs proved to be sensitive enough to capture weak CPM effects elicited by a conditioning stimulus of rather low noxious load. The usage of such mild noxious conditioning stimuli-in contrast to stimuli of higher noxious load (e.g., cold pressor test)-has the advantage that the activation of other types of pain inhibitory mechanisms in parallel (like attentional distraction, stress-induced analgesia) can be avoided.
    Somatosensory & Motor Research 02/2014; 31(2). DOI:10.3109/08990220.2014.887562 · 0.58 Impact Factor
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    • "We tried to decrease the variability by using uniform 'conditioning-stimuli' because the effect of the 'conditioningstimulus' on the CPM response has already been demonstrated. Granot et al. [24] showed a positive correlation between the CPM responses induced by two types of 'conditioning-stimuli'. Two other studies revealed higher CPM responses for the cold pressor test as compared to muscle pain, mechanical pain, or tourniquet pain [25] [26]. "
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    ABSTRACT: Background and purposeConditioned pain modulation (CPM) is a testing paradigm representing features of diffuse noxious inhibitory control. There is large diversity in the paradigms applied to induce CPM, and the consistency in CPM responses assessed by different paradigms is largely unknown. We aimed to characterize and explore the associations between the CPM responses assessed by different paradigms in the same cohort.Methods Thirty-three healthy middle-aged subjects underwent six CPM paradigms. The ‘test-stimuli’, consisted of thermal and mechanical modalities, using pain thresholds, suprathreshold pain and temporal summation types of measurements. The ‘conditioning-stimulus’ consisted of a contact heat stimulus applied to the thener of the left hand for 60 s at an intensity of 46.5 °C.ResultsLarge variability was observed among the responses to the different CPM paradigms. Surprisingly, no correlations were found between the various CPM responses.Conclusions The variability in the CPM responses may suggest that the capacity of pain modulation is a multifaceted trait, whose expression varies with the application of different CPM paradigms.ImplicationsConsidering that CPM responses may represent different processes when assessed by different paradigms, we encourage the use of more than one CPM paradigm.
    Scandinavian Journal of Pain 01/2013; 4(1):10–14. DOI:10.1016/j.sjpain.2012.08.001
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    • "A negative value indicated efficient CPM. This paradigm of conditioned pain modulation is routinely used in our laboratory [10] [18] [25] [28]. The mean pain score of the stand-alone 'test stimulus' pain also served as a measure of supra-threshold tonic heat pain. "
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    ABSTRACT: This study aims to individualize the selection of drugs for neuropathic pain by examining the potential coupling of a given drug's mechanism of action with the patient's pain modulation pattern. The latter is assessed by the conditioned pain modulation (CPM) and temporal summation (TS) protocols. We hypothesized that patients with a malfunctioning pain modulation pattern, such as less efficient CPM, would benefit more from drugs augmenting descending inhibitory pain control than would patients with a normal modulation pattern of efficient CPM. Thirty patients with painful diabetic neuropathy received 1 week of placebo, 1 week of 30 mg/d duloxetine, and 4 weeks of 60 mg/d duloxetine. Pain modulation was assessed psychophysically, both before and at the end of treatment. Patient assessment of drug efficacy, assessed weekly, was the study's primary outcome. Baseline CPM was found to be correlated with duloxetine efficacy (r=0.628, P<.001, efficient CPM is marked negative), such that less efficient CPM predicted efficacious use of duloxetine. Regression analysis (R(2)=0.673; P=.012) showed that drug efficacy was predicted only by CPM (P=.001) and not by pretreatment pain levels, neuropathy severity, depression level, or patient assessment of improvement by placebo. Furthermore, beyond its predictive value, the treatment-induced improvement in CPM was correlated with drug efficacy (r=-0.411, P=.033). However, this improvement occurred only in patients with less efficient CPM (16.8±16.0 to -1.1±15.5, P<.050). No predictive role was found for TS. In conclusion, the coupling of CPM and duloxetine efficacy highlights the importance of pain pathophysiology in the clinical decision-making process. This evaluative approach promotes personalized pain therapy.
    Pain 04/2012; 153(6):1193-8. DOI:10.1016/j.pain.2012.02.021 · 5.84 Impact Factor
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