The journal of pain : official journal of the American Pain Society
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Quantification of the human painful sensory experience is an essential step in the translation of knowledge from animal nociception to human pain. Translational models for assessment of pain are very important, as such models can be used in: 1) basic mechanistic studies in healthy volunteers; 2) clinical studies for diagnostic and monitoring purposes; 3) pharmacological studies to evaluate analgesic efficacy of new and existing compounds. Quantitative pain assessment, or quantitative sensory testing (QST), provides psychophysical methods that systematically document alterations and reorganization in nervous system function and, in particular, the nociceptive system. QST is defined as the determination of thresholds or stimulus response curves for sensory processing under normal and pathophysiological conditions. The modern concept of advanced QST for experimental pain assessment is a multimodality, multitissue approach where different pain modalities (thermal, mechanical, electrical, and chemical) are applied to different tissues (skin, muscles, and viscera) and the responses are assessed by psychophysical methods (thresholds and stimulus-response functions). Many new and advanced technologies have been developed to help relieve evoked, standardized, and painful reactions. Assessing pain has become a question of solving a multi-input, multi-output problem, with the solution providing the possibility of teasing out which pain pathways and mechanisms are involved, impaired, or affected. ⋯ Many methodologies have been developed for quantitative assessment of pain perception and involved mechanisms. This paper describes the background for the different methods, the use in basic pain experiments on healthy volunteers, how they can be applied in drug profiling, and the applications in clinical practice.
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Recent evidence points to an association between experimental pain measures obtained preoperatively and acute postoperative pain (POP). We hypothesized that pain temporal summation (TS) might be an additional predictor for POP insofar as it represents the neuroplastic changes that occur in the central nervous system following surgery. Therefore, a wide range of psychophysical tests (TS to heat and mechanical repetitive stimuli, pain threshold, and suprathreshold pain estimation) and personality tests (pain catastrophizing and anxiety levels) were administered prior to thoracotomy in 84 patients. POP ratings were evaluated on the 2nd and 5th days after surgery at rest (spontaneous pain) and in response to activity (provoked pain). Linear regression models revealed that among all assessed variables, enhanced TS and higher pain scores for mechanical stimulation were significantly associated with greater provoked POP intensity (overall r2 = 0.225, P = .008). Patients who did not demonstrate TS to both modalities reported lower scores of provoked POP as compared with patients who demonstrated TS in response to at least 1 modality (F = 4.59 P = .013). Despite the moderate association between pain catastrophizing and rest POP, none of the variables predicted the spontaneous POP intensity. These findings suggest that individual susceptibility toward a greater summation response may characterize patients who are potentially vulnerable to augmented POP. ⋯ This study proposed the role of pain temporal summation assessed preoperatively as a significant psychophysical predictor for acute postoperative pain intensity. The individual profile of enhanced pain summation is associated with the greater likelihood of higher postoperative pain scores.
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Fibromyalgia (FM) has been associated with alterations in brain morphometry and abnormal dopaminergic neurotransmission. Evidence from preclinical models has demonstrated that dopamine plays a role in promoting neuronal integrity. We therefore sought to confirm previous findings of reduced gray matter density in subjects with FM and to determine whether variations in dopamine metabolism might affect gray matter density. Voxel-based morphometry was used to evaluate anatomical magnetic resonance imaging data from 30 female FM subjects in comparison with 20 age- and gender-matched healthy control subjects. In addition, data from a subset of subjects from both groups who had previously participated in our positron emission tomography study using radiolabeled DOPA (n = 14; 6 FM subjects and 8 control subjects) was used to determine whether correlation might exist between gray matter density and dopamine metabolism. We found a significant reduction in gray matter density within the bilateral parahippocampal gyri, right posterior cingulate cortex, and left anterior cingulate cortex. In addition, a positive correlation was demonstrated between an index of dopamine metabolism from the ventral tegmental area wherein cell bodies of corticolimbic projection neurons originate and gray matter density, specifically in the bilateral parahippocampal gyri and left pregenual cortex. The current results confirm our previous findings that FM is associated with altered brain morphometry. Alterations in dopamine metabolism might contribute to the associated changes in gray matter density. ⋯ Fibromyalgia is associated with reductions in gray matter density within brain regions ostensibly involved in phenomena related to the disorder, including enhanced pain perception, cognitive dysfunction, and abnormal stress reactivity. Given mounting evidence of abnormal dopaminergic neurotransmission associated with the disorder, the strong correlation between dopamine metabolism and gray matter density provides insight as to the pathophysiology that might contribute to these changes.
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Neuropathic pain (NP) is a difficult issue, particularly in cancer which is a dynamic condition where multiple pain etiologies are concomitantly present. Cancer pain is often labeled as mixed mechanism pain and is not easily classified as exclusively nociceptive or NP. The aim of this study was to explore the value of evaluation tools such as Neuropathic Pain Questionnaire (NPQ), complete and short form (NPQ-SF), Leeds Assessment of Neuropathic Signs and Symptoms (LANSS) and Neuropathic Pain Symptom Inventory (NPSI). The secondary outcome was to evaluate the response to opioid titration, according to the hierarchical classification of definite, possible and unlikely NP. A consecutive sample of patients referred for treatment of cancer-related pain were eligible for participation in the study. The inclusion criterion was uncontrolled cancer pain requiring adjustment of opioid therapy. Patients were clinically classified into tertiles based according to graded evidence of nervous system lesion: definite NP, possible NP, or unlikely NP. Pain and symptoms intensities were measured before (T0) and at the end of opioid titration (T1). Patients were titrated with escalating doses of opioids, supported by symptomatic drugs, changing the route of administration, or by opioid switching according to the clinical response. At T1 the opioid response was clinically graded from 1 to 4. Opioid escalation index was calculated. A single independent investigator, blinded to the clinical assessment and treatment, collected data from NPQ, NPQ-SF, LANSS Pain Scale, and NPSI. One hundred and sixty-seven patients concluded the study. Sixty, thirty-six, and seventy-one patients were clinically assessed as having definite NP, possible NP, or unlikely NP, respectively. A relationship between the values of the assessment tools and clinician rating was found. Patients with the highest values of assessment tools were also more likely to be clinically labeled as definite NP, although sensibility and specificity were low. Patients with a clinical diagnosis of definite NP, possible NP, or unlikely NP showed significant differences in opioid response (P < .0005). Patients with "unlikely NP" had a lower pain intensity at T1 (P < .05), and patients with "definite NP" required more intensive treatment. Patients requiring more aggressive treatment showed significantly higher values of Opioid Escalation Index (OEI)mg. ⋯ Screening tools may provide a basis to suggest a common language in cancer pain syndromes. A hierarchical grouping seems to be more flexible and fits cancer patient characteristics. This study also confirms that opioids are clinically effective in "definite NP" conditions although a more aggressive treatment requiring careful utilization of opioids and symptomatic drugs is strictly necessary.
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Comparative Study
Comparison of oxaliplatin- and cisplatin-induced painful peripheral neuropathy in the rat.
Although platinum-based cancer chemotherapies produce painful peripheral neuropathy as dose-limiting side effects, there are important differences in the pain syndromes produced by members of this class of drugs. In the rat, cisplatin-induced hyperalgesia has latency to onset of 24 to 48 hours, is maximal by 72 to 96 hours, and is attenuated by inhibitors of caspase signaling but not by inhibitors of the mitochondrial electron transport chain (mETC) and antioxidants. In contrast, oxaliplatin-induced mechanical hyperalgesia is already present by 5 minutes and peaks by 20 minutes. Whereas oxaliplatin hyperalgesia persists for weeks, starting around day 10 to 15, its severity decreases to a lower 2nd plateau level. The rapid-onset 1st plateau in oxaliplatin-induced hyperalgesia was characterized by prominent cold allodynia and in contrast to cisplatin was attenuated by inhibitors of the mETC and antioxidants but not inhibitors of caspase signaling. However, tested later during the 2nd plateau, it was characterized by less intense hyperalgesia and no cold allodynia and was attenuated by inhibitors of caspase signaling as well as by inhibitors of the mETC and by antioxidants. ⋯ The findings of this study distinguish between the neuropathic pain syndromes produced by members of a single chemical class of anticancer drugs and suggest that the underlying mechanisms of various forms of peripheral neuropathy may be different. Further, it defines the need for selective therapy for different types of neuropathy.