Philippe Goffaux

widespread pain in fibromyalgia is related to a deficit of endogenous pain inhibition

&NA; A deficit of endogenous pain inhibitory systems has been suggested to contribute to some chronic pain conditions, one of them being fibromyalgia. The aim of the investigation was to test whether endogenous pain inhibitory systems were activated by a spatial summation procedure in 30 fibromyalgia, 30 chronic low back pain, and 30 healthy volunteers who participated in a cross‐over trial (two sessions). Each session consisted of visual analog scale ratings of pain during the immersion of different surfaces of the arm in circulating noxious cold (12 °C) water. The arm was arbitrarily divided into eight segments from the fingertips to the shoulder. One session was ascending (from the fingertips to the shoulder) and the other was descending (from the shoulder to the fingertips); they included eight consecutive 2‐min immersions separated by 5‐min resting periods. For healthy and low back pain subjects, pain was perceived differently during the ascending and descending sessions (P=0.0001). The descending session resulted in lower pain intensity and unpleasantness. This lowering of the perception curve seems to be due to a full recruitment of inhibitory systems at the beginning of the descending session as opposed to a gradual recruitment during the ascending session. For fibromyalgia subjects, no significant differences were found between the increasing and decreasing sessions (P>0.05). These data support a deficit of endogenous pain inhibitory systems in fibromyalgia but not in chronic low back pain. The treatments proposed to fibromyalgia patients should aim at stimulating the activity of those endogenous systems.

Descending analgesia – When the spine echoes what the brain expects

Abstract Changes in pain produced by psychological factors (e.g., placebo analgesia) are thought to result from the activity of specific cortical regions. However, subcortical nuclei, including the periaqueductal gray and the rostroventral medulla, also show selective activation when subjects expect pain relief. These brainstem regions send inhibitory projections to the spine and produce diffuse analgesic responses. Regrettably the precise contribution of spinal mechanisms in predicting the strength of placebo analgesia is unknown. Here, we show that expectations regarding pain radically change the strength of spinal nociceptive responses in humans. We found that contrary to expectations of analgesia, expectations of hyperalgesia completely blocked the analgesic effects of descending inhibition on spinal nociceptive reflexes. Somatosensory‐evoked brain potentials and pain ratings further confirmed changes in spino‐thalamo‐cortical responses consistent with expectations and with changes in the spinal response. These findings provide direct evidence that the modulation of pain by expectations is mediated by endogenous pain modulatory systems affecting nociceptive signal processing at the earliest stage of the central nervous system. Expectation effects, therefore, depend as much about what takes place in the spine as they do about what takes place in the brain. Furthermore, complete suppression of the analgesic response normally produced by descending inhibition suggests that anti‐analgesic expectations can block the efficacy of pharmacologically valid treatments which has important implications for clinical practice.

Changes in pain perception and descending inhibitory controls start at middle age in healthy adults.

ObjectivesPrevious studies have shown a reduction of diffuse noxious inhibitory controls (DNICs) in elderly adults compared with younger adults. Unfortunately, little is known regarding the developmental course of DNIC deficits and so it is still unclear whether middle-aged adults also show a DNIC deficit. The aims of the present study were to better characterize the developmental time course of the change in DNIC response by adding a middle-aged group. The role of expectations was also investigated. MethodsThe pain thresholds (PTs) of 20 young, 20 middle-aged, and 20 healthy elderly volunteers were assessed before and during a cold pressor task (water at 7°C). Acute nociceptive stimuli were administered using a thermode and consisted of a range of painless and painful heat pulses. ResultsAnalyses showed that thermal PTs increase by middle age but that the DNIC-induced increase in PT dampens progressively with advancing age. DNIC response was negatively correlated with advancing age, however, expectations regarding DNIC efficacy did not vary with age. This suggests that age-related changes in the size of the DNIC response are not best explained by an age-related change in expectation. DiscussionThe findings tell us that changes in pain perception and endogenous pain modulation arrive earlier than previously suggested. Studies on aging and pain should include a middle-aged group when comparing pain measures across the adult lifespan.

An experimental model to measure excitatory and inhibitory pain mechanisms in humans.

Numerous approaches have been used to induce and measure experimental pain perception with the goal of better understanding excitatory and inhibitory pain mechanisms. In this study, the objective was to develop a simple experimental design which would enable us to elicit and measure multiple nociceptive mechanisms that have been reported to play a role in the development and persistency of chronic pain, such as temporal summation (TS) and diffuse noxious inhibitory control (DNIC). Eighty-three healthy subjects (42 men, 41 women) participated in this study where we examined pain perception of two tonic heat pain stimulation (thermode) separated by a 2 minute cold pressor test (CPT) (7 degrees C, 10 degrees C or 12 degrees C) which allowed us to activate DNIC. The heat pain response was characterized by a peak pain during the first 30 s, which was stronger for women (p = 0.001). We also observed a TS phenomenon during the second minute of stimulation. DNICs analgesia was assessed by measuring the difference in pain ratings between the two thermode procedures, before and after inducing DNIC by a cold pressure test on the opposite arm. We found that the mean pain ratings and peak pain but not TS were significantly reduced by DNIC. No sex differences were observed in DNIC analgesia. Our experimental pain design allowed us to measure several excitatory and inhibitory pain mechanisms in one experimental session. We were able to separate the effect of DNIC on the peak pain and on TS. This method is simple, sensitive and can easily be used in different population of either healthy subjects or chronic pain patients.

The Deficit of Pain Inhibition in Fibromyalgia Is More Pronounced in Patients With Comorbid Depressive Symptoms

BackgroundOn pathophysiologic grounds, fibromyalgia (FM) is characterized by a deficit in diffuse noxious inhibitory controls (DNIC), but the role of depressive symptoms on these mechanisms has not been investigated. We hypothesized that the deficit in pain inhibition would be more pronounced in FM patients with depressive symptoms (FM+D), relative to patients without such symptoms (FM−D). MethodsFifty-two women diagnosed with FM (American College of Rheumatology criteria) and 10 healthy women participated in this study. Thermal stimuli were used to measure pain thresholds and DNIC efficacy (spatial summation paradigm). Clinical pain was measured using visual analog scales. ResultsWe found that the amplitude of DNIC was smaller in FM+D patients, relative to the FM−D group; and that daily pain (unpleasantness) was higher in the FM+D group, relative to FM−D patients. DiscussionWe found that FM+D patients have a more pronounced deficit in pain inhibition as well increased clinical pain. As such, these results show the usefulness of combining psychologic factors and psychophysical measures to identify subgroups of FM patients. These results may have implications for future treatment of FM patients with and without comorbid depressive symptoms.

Preterm births: Can neonatal pain alter the development of endogenous gating systems?

Prematurity is known to affect the development of various neurophysiological systems, including the maturation of pain and cardiac circuits. The purpose of this study was to see if numerous painful interventions, experienced soon after birth, affect counterirritation‐induced analgesia (triggered using the cold pressor test) later in life. A total of 26 children, between the ages of 7 and 11 participated in the study. Children were divided into three groups, according to their birth status (i.e., term‐born, born preterm and exposed to numerous painful interventions, or born preterm and exposed to few painful interventions). Primary outcome measures were heat pain thresholds, heat sensitivity scores, and cardiac reactivity. Results showed that preterm children and term‐born children had comparable pain thresholds. Exposure to conditioning cold stimulation significantly increased heart rate and significantly decreased the thermal pain sensitivity of term‐born children. These physiological reactions were also observed among preterm children who were only exposed to a few painful interventions at birth. Changes in heart rate and pain sensitivity in response to conditioning cold stimulation were not observed in preterm children that had been exposed to numerous painful procedures during the neonatal period. These results suggest that early pain does not lead to enhanced pain sensitivity when premature babies become children, but that their endogenous pain modulatory mechanisms are not as well developed as those of children not exposed to noxious insult at birth. Greater frequency of painful procedures also dampened the rise in heart rate normally observed when experimental pain is experienced.

Fibromyalgia subgroups: profiling distinct subgroups using the Fibromyalgia Impact Questionnaire. A preliminary study.

The main goal of this project was to identify the presence of fibromyalgia (FM) subgroups using a simple and frequently used clinical tool, the Fibromyalgia Impact Questionnaire (FIQ). A total of 61 women diagnosed with FM participated in this study. FM subgroups were created by applying a hierarchical cluster analysis on selected items of the FIQ (pain, fatigue, morning tiredness, stiffness, anxiety and depressive symptoms). We also tested for group differences on experimental pain, psychosocial functioning and demographic characteristics. Two cluster profiles best fit our data. FM-Type I was characterized by the lowest levels of anxiety, depressive and morning tiredness symptoms, while FM-Type II was characterized by elevated levels of pain, fatigue, morning tiredness, stiffness, anxiety and depressive symptoms. Both FM subgroups showed hyperalgesic responses to experimental pain. These results suggest that pain and stiffness are universal symptoms of the disorder but that psychological distress is a feature present only in some patients.

Evidence of descending inhibition deficits in atypical but not classical trigeminal neuralgia.

ABSTRACT Trigeminal neuralgia (TN) is a rare neuropathic facial pain disorder. Two forms of TN, classical TN (CTN) and atypical TN (ATN), are reported and probably have different aetiologies. The aim of the present study was to evaluate the functional integrity of the diffuse noxious inhibitory controls (DNIC) in (1) a group of patients with classical trigeminal neuralgia (CTN), (2) a group of patients with atypical trigeminal neuralgia (ATN), and (3) a group of healthy controls in order to determine if a descending pain modulation deficit could participate in the pathophysiology of TN pain. DNIC responses of 14 CTN patients, 14 ATN patients and 14 healthy controls were obtained by comparing thermode‐induced facial heat pain scores before and after activating DNIC. DNIC was triggered using a standard counter–irritation paradigm (i.e., immersion of the arm in painfully cold water). General sensitivity to pain was also evaluated by measuring mechanical pain thresholds over 18 points located outside the trigeminal territory. Healthy participants and CTN patients showed a 21% and 16% reduction in thermode‐induced pain following the immersion, respectively (all p‐values <.01), whereas ATN patients experienced no change (p = .57). ATN patients also had more tender points (mechanical pain thresholds <4.0 kg) than CTN and healthy controls (all p‐values <.05). Taken together, these results suggest that the underlying physiopathology differs between CTN and ATN and that a deficit in descending inhibition may further contribute to the pain experienced by patients with ATN.

Deciphering the role of endogenous opioids in high frequency TENS using low and high doses of naloxone

&NA; Previous human studies have shown that the analgesic effect of high‐frequency TENS could not be reversed by low doses of naloxone. The aim of the present study was to reinvestigate the possible contribution of opioid receptors to high‐frequency TENS analgesia by using low (0.02 mg/kg) and high (0.14 mg/kg) doses of naloxone. Naloxone (high and low doses) and saline were administered intravenously to young healthy adults using a triple‐blind randomized cross‐over design. For each visit, TENS (100 Hz, 60 &mgr;s) was applied for 25 min to the external surface of the left ankle. TENS intensity was adjusted to obtain strong but comfortable (innocuous) paresthesias. Experimental pain was evoked with a 1 cm2 thermode applied on the lateral aspect of the left heel. Subjective pain scores were obtained before, during and after TENS. Because preliminary analyses showed that the order of presentation affected the pattern of results, only the first visit of every participant could be analyzed without fear of contamination from possible carry‐over effects. These revealed that TENS maintained its analgesic properties following the injection of saline (p < .001) and the injection of a low dose of naloxone (p < .05). However, when a high dose of naloxone was administered, TENS analgesia was completely blocked (p = .20). These results suggest that high‐frequency TENS involves opioid receptors. An insufficient amount of opioid antagonist likely prevented previous human studies from discovering the importance of opioid receptors in producing high‐frequency TENS analgesia.

Pain relief through expectation supersedes descending inhibitory deficits in fibromyalgia patients

ABSTRACT In healthy adults, expectations can modulate the activity of inhibitory bulbo‐spinal projections, and can even block the analgesic properties of counter‐irritation – a phenomenon that triggers descending inhibition. Since descending inhibition is known to be deficient in fibromyalgia (FM) patients, we tested the possibility that expectancy‐mediated analgesia would improve, or even kick‐start, the deficient inhibitory responses of FM patients. By measuring subjective pain ratings, spinal withdrawal reflexes, and somatosensory evoked potentials (SEP), it was possible to test whether or not expectancy‐mediated analgesia involved descending inhibition in FM patients. Here, we show that expectations of analgesia radically change the subjective experience of pain, but do not eliminate evidence of spinal hyperexcitability in FM patients. We found that expectations of analgesia reduce subjective pain ratings and decrease SEP amplitudes, confirming that expectations influence thalamocortical processes. However, even when analgesia was experienced, the spinal activity of FM patients was abnormal, showing heightened reflex responses. This demonstrates that, unlike healthy subjects, the modulation of pain by expectations in FM fails to influence spinal activity. These results indicate that FMs are capable of expectancy‐induced analgesia but that, for them, this form of analgesia does not depend on the recruitment of descending inhibitory projections.