Abstract
ABSTRACT Background: Temporal summation and conditioned pain modulation (CPM) can be measured using a thermode and cold pressor test (CPTest). Unfortunately, these complex and expensive tools are ill-suited for routine clinical assessments. Aims: We aimed to compare the temporal summation and CPM obtained with the thermode + CPTest paradigm to those obtained with a novel paradigm using transcutaneous electrical nerve stimulation (TENS). Methods: We assessed temporal summation and CPM in 29 healthy participants, using two paradigms (random order): TENS, and thermode + CPTest. In the TENS paradigm, both the conditioning stimulus (CS) and the test stimulus (TS) were delivered using TENS; in the thermode + CPTest paradigm, the CS consisted of a CPTest and the TS was delivered using a thermode. We compared the average temporal summation and CPM evoked by the two paradigms. Results: Average temporal summation was similar for both modalities (P = 0.90), and the number of participants showing temporal summation was similar in both paradigms (19 with thermode vs. 18 with TENS; P = 1.00). Average CPM response was larger following the thermode + CPTest than following the TENS (P = 0.005), and more participants showed CPM with the thermode + CPTest paradigm compared to the TENS paradigm (24 vs. 14; P = 0.01). Conclusions: Both paradigms were roughly equivalent in the ability to evoke temporal summation (although response to one modality did not predict response to the other), but the TENS paradigm appeared to be less apt to induce a CPM response than the thermode + CPTest paradigm.
Highlights
Human studies, where such electro-neurophysiological measurements are much more difficult to obtain, often rely on behavioral correlates of these endogenous pain control mechanisms: for excitatory mechanisms, a phenomenon called “temporal summation” is often measured, wherein perceived pain intensity increases throughout a repetitive noxious stimulation of fixed intensity10,11; for inhibitory mechanisms, the concept of conditioned pain modulation (CPM) was developed, wherein a noxious stimulation induces widespread hypoalgesia
Six of these participants were later excluded for various reasons: failure to attend the second session; mild adverse reaction to transcutaneous electrical nerve stimulation (TENS); no pain felt during TENS; history of nonefficacy with TENS; inability to withstand the cold pressor test (CPTest) for more than 15 s; and undisclosed neurocognitive disorder
Our results suggest that the average pain intensity induced during the pre-conditioning stimulus (CS) test stimulus (TS) was higher with the thermode than with the TENS (54 ± 16/100 and 39 ± 21/100, respectively; P = 0.007)
Summary
Chronic pain affects approximately one-fifth of the general population, including one-third of the elderly population. A number of chronic pain conditions are characterized by imbalances in endogenous excitatory and/or inhibitory mechanisms of pain modulation. Animal studies have identified the specific electro-neurophysiological correlates of some of these mechanisms, such as wind-up (an excitatory mechanism of pain characterized by a progressive increase in dorsal horn activity observed following repeated C-fiber activation) and diffuse noxious inhibitory controls (an endogenous inhibitory mechanism of pain characterized by the activation of descending inhibitory projections from brainstem structures following a noxious stimulation, resulting in decreased reponses of spinal cord neurons). Human studies, where such electro-neurophysiological measurements are much more difficult to obtain, often rely on behavioral correlates of these endogenous pain control mechanisms: for excitatory mechanisms, a phenomenon called “temporal summation” is often measured, wherein perceived pain intensity increases throughout a repetitive noxious stimulation of fixed intensity; for inhibitory mechanisms, the concept of conditioned pain modulation (CPM) was developed, wherein a noxious stimulation induces widespread hypoalgesia.12,13Imbalances in these endogenous pain modulation mechanisms (often in the form of increased temporal summation and/or decreased CPM, which both result in greater overall pain intensity) appear to correlate with response to certain treatments. For instance, patients with chronic pancreatitis presenting increased temporal summation respond preferentially to pregabalin, and patients with diabetic neuropathy presenting decreased CPM respond preferentially to duloxetine. Evaluating these mechanisms among people suffering from chronic pain could allow clinicians to adapt the treatment to each patient according to the deficits observed. A paradigm often used to assess CPM consists of a test stimulus (TS) administered before and after a conditioning stimulus (CS); CPM is measured by calculating the difference in pain levels elicited by the TS before and after the CS. Our team has developed a slightly modified version of this paradigm that allows for the assessment of temporal summation as well as CPM, by measuring temporal summation throughout the first TS. In this modified CPM paradigm, the TS consists of a sustained moderately painful heat stimulation delivered for 120 s using a thermode and the CS consists of a cold pressor test (CPTest) wherein subjects immerse their dominant forearm in a cold water bath (10°C) for 120 s. Animal studies have identified the specific electro-neurophysiological correlates of some of these mechanisms, such as wind-up (an excitatory mechanism of pain characterized by a progressive increase in dorsal horn activity observed following repeated C-fiber activation) and diffuse noxious inhibitory controls (an endogenous inhibitory mechanism of pain characterized by the activation of descending inhibitory projections from brainstem structures following a noxious stimulation, resulting in decreased reponses of spinal cord neurons).8,9 Human studies, where such electro-neurophysiological measurements are much more difficult to obtain, often rely on behavioral correlates of these endogenous pain control mechanisms: for excitatory mechanisms, a phenomenon called “temporal summation” is often measured, wherein perceived pain intensity increases throughout a repetitive noxious stimulation of fixed intensity; for inhibitory mechanisms, the concept of conditioned pain modulation (CPM) was developed, wherein a noxious stimulation induces widespread hypoalgesia.. Conclusions: Both paradigms were roughly equivalent in the ability to evoke temporal summation ( response to one modality did not predict response to the other), but the TENS paradigm appeared to be less apt to induce a CPM response than the thermode + CPTest paradigm
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