Psychophysical evaluation of endogenous pain inhibition via conditioned pain modulation (CPM) represents a new generation of laboratory tests for pain assessment. In this review we discuss recent ...findings on CPM in neuropathic pain and refer to psychophysical, neurophysiological, and methodological aspects of its clinical implications. Typically, chronic neuropathic pain patients express less efficient CPM, to the extent that incidence of acquiring neuropathic pain (e.g. post-surgery) and its intensity can be predicted by a pre-surgery CPM assessment. Moreover, pre-treatment CPM evaluation may assist in the correct choice of serotonin-noradrenalin reuptake inhibitor analgesic agents for individual patients. Evaluation of pain modulation capabilities can serve as a step forward in individualizing pain medicine.
Conditioned pain modulation (CPM) predicts efficacy of duloxetine in painful diabetic neuropathy; patients with less efficient CPM are more likely to benefit from the drug.
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 1week of placebo, 1week of 30mg/d duloxetine, and 4weeks of 60mg/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 (R2=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 variability can be partially attributed to psycho-cognitive features involved in its processing. However, accumulating research suggests that simple linear correlation between situational and ...dispositional factors may not be sufficiently explanatory, with some positing a role for mediating influences. In addition, acute pain processing studies generally focus on a post-operative model with less attention provided to post-traumatic injury. As such, this study aimed to investigate a more comprehensive pain processing model that included direct and indirect associations between acute pain intensity in the head and neck, pain catastrophizing (using pain catastrophizing scale (PCS)), and pain sensitivity (using the pain sensitivity questionnaire (PSQ)), among 239 patients with post-motor vehicle collision pain. The effect of personality traits (using Ten Items Personality Inventory (TIPI)) and emotional status (using Hospital Anxiety and Depression Scale (HADS) and Perceived Stress Scale (PSS)) on that model was examined as well. To this end, three Structural Equation Modeling (SEM) analyses were conducted. Overall, the data had good fit to all the models, with only PSQ found to have a direct correlation with acute pain intensity. The SEM analyses conversely revealed several mediations. Specifically, that: first, PSQ fully mediated the relationship between PCS and pain intensity; second, PCS and PSQ together fully mediated the relationship between conscientiousness (personality trait) and pain intensity; and finally, emotional status had direct and indirect links with PSQ and pain intensity. In conclusion, these models suggest that during the acute post-collision phase, pain sensitivity intermediates between emotional states and personality traits, partially via elevated pain catastrophizing thoughts.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Surgical and medical procedures, mainly those associated with nerve injuries, may lead to chronic persistent pain. Currently, one cannot predict which patients undergoing such procedures are ‘at ...risk’ to develop chronic pain. We hypothesized that the endogenous analgesia system is key to determining the pattern of handling noxious events, and therefore testing diffuse noxious inhibitory control (DNIC) will predict susceptibility to develop chronic post-thoracotomy pain (CPTP). Pre-operative psychophysical tests, including DNIC assessment (pain reduction during exposure to another noxious stimulus at remote body area), were conducted in 62 patients, who were followed 29.0
±
16.9 weeks after thoracotomy. Logistic regression revealed that pre-operatively assessed DNIC efficiency and acute post-operative pain intensity were two independent predictors for CPTP. Efficient DNIC predicted lower risk of CPTP, with OR 0.52 (0.33–0.77 95% CI,
p
=
0.0024), i.e., a 10-point numerical pain scale (NPS) reduction halves the chance to develop chronic pain. Higher acute pain intensity indicated OR of 1.80 (1.28–2.77,
p
=
0.0024) predicting nearly a double chance to develop chronic pain for each 10-point increase. The other psychophysical measures, pain thresholds and supra-threshold pain magnitudes, did not predict CPTP. For prediction of acute post-operative pain intensity, DNIC efficiency was not found significant. Effectiveness of the endogenous analgesia system obtained at a pain-free state, therefore, seems to reflect the individual’s ability to tackle noxious events, identifying patients ‘at risk’ to develop post-intervention chronic pain. Applying this diagnostic approach before procedures that might generate pain may allow individually tailored pain prevention and management, which may substantially reduce suffering.
MRI-based resting-state functional connectivity (rsFC) has been shown to predict response to pharmacological and non-pharmacological treatments for chronic pain, but not yet for motor cortex ...transcranial magnetic stimulation (M1-rTMS). Twenty-seven fibromyalgia syndrome (FMS) patients participated in this double-blind, crossover, and sham-controlled study. Ten daily treatments of 10 Hz M1-rTMS were given over 2 weeks. Before treatment series, patients underwent resting-state fMRI and clinical pain evaluation. Significant pain reduction occurred following active, but not sham, M1-rTMS. The following rsFC patterns predicted reductions in clinical pain intensity after the active treatment: weaker rsFC of the default-mode network with the middle frontal gyrus (r = 0.76, p < 0.001), the executive control network with the rostro-medial prefrontal cortex (r = 0.80, p < 0.001), the thalamus with the middle frontal gyrus (r = 0.82, p < 0.001), and the pregenual anterior cingulate cortex with the inferior parietal lobule (r = 0.79, p < 0.001); and stronger rsFC of the anterior insula with the angular gyrus (r = - 0.81, p < 0.001). The above regions process the attentional and emotional aspects of pain intensity; serve as components of the resting-state networks; are modulated by rTMS; and are altered in FMS. Therefore, we suggest that in FMS, the weaker pre-existing interplay between pain-related brain regions and networks, the larger the pain relief resulting from M1-rTMS.
Experimental pain stimuli can be used to simulate patients' pain experience. We review recent developments in psychophysical pain testing, focusing on the application of the dynamic tests-conditioned ...pain modulation (CPM) and temporal summation (TS). Typically, patients with clinical pain of various types express either less efficient CPM or enhanced TS, or both. These tests can be used in prediction of incidence of acquiring pain and of its intensity, as well as in assisting the correct choice of analgesic agents for individual patients. This can help to shorten the commonly occurring long and frustrating process of adjusting analgesic agents to the individual patients. We propose that evaluating pain modulation can serve as a step forward in individualizing pain medicine.
Endogenous analgesic mechanisms are intrinsically associated with the spatial and temporal filtering of afferent input and play a far greater role than simple gain modulation.
The role of endogenous ...analgesic mechanisms has largely been viewed in the context of gain modulation during nociceptive processing. However, these analgesic mechanisms may play critical roles in the extraction and subsequent utilization of information related to spatial and temporal features of nociceptive input. To date, it remains unknown if spatial and temporal filtering of nociceptive information is supported by similar analgesic mechanisms. To address this question, human volunteers were recruited to assess brain activation with functional magnetic resonance imaging during conditioned pain modulation (CPM) and offset analgesia (OA). CPM provides one paradigm for assessing spatial filtering of nociceptive information while OA provides a paradigm for assessing temporal filtering of nociceptive information. CPM and OA both produced statistically significant reductions in pain intensity. However, the magnitude of pain reduction elicited by CPM was not correlated with that elicited by OA across different individuals. Different patterns of brain activation were consistent with the psychophysical findings. CPM elicited widespread reductions in regions engaged in nociceptive processing such as the thalamus, insula, and secondary somatosensory cortex. OA produced reduced activity in the primary somatosensory cortex but was associated with greater activation in the anterior insula, dorsolateral prefrontal cortex, intraparietal sulcus, and inferior parietal lobule relative to CPM. In the brain stem, CPM consistently produced reductions in activity, while OA produced increases in activity. Conjunction analysis confirmed that CPM-related activity did not overlap with that of OA. Thus, dissociable mechanisms support inhibitory processes engaged during spatial vs temporal filtering of nociceptive information.
Sensory modulation disorder (SMD) affects sensory processing across single or multiple sensory systems. The sensory over-responsivity (SOR) subtype of SMD is manifested clinically as a condition in ...which non-painful stimuli are perceived as abnormally irritating, unpleasant, or even painful. Moreover, SOR interferes with participation in daily routines and activities (Dunn, 2007; Bar-Shalita et al., 2008; Chien et al., 2016), co-occurs with daily pain hyper-sensitivity, and reduces quality of life due to bodily pain. Laboratory behavioral studies have confirmed abnormal pain perception, as demonstrated by hyperalgesia and an enhanced lingering painful sensation, in children and adults with SMD. Advanced quantitative sensory testing (QST) has revealed the mechanisms of altered pain processing in SOR whereby despite the existence of normal peripheral sensory processing, there is enhanced facilitation of pain-transmitting pathways along with preserved but delayed inhibitory pain modulation. These findings point to central nervous system (CNS) involvement as the underlying mechanism of pain hypersensitivity in SOR. Based on the mutual central processing of both non-painful and painful sensory stimuli, we suggest shared mechanisms such as cortical hyper-excitation, an excitatory-inhibitory neuronal imbalance, and sensory modulation alterations. This is supported by novel findings indicating that SOR is a risk factor and comorbidity of chronic non-neuropathic pain disorders. This is the first review to summarize current empirical knowledge investigating SMD and pain, a sensory modality not yet part of the official SMD realm. We propose a neurophysiological mechanism-based model for the interrelation between pain and SMD. Embracing the pain domain could significantly contribute to the understanding of this condition's pathogenesis and how it manifests in daily life, as well as suggesting the basis for future potential mechanism-based therapies.
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