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Background: We aimed to perform the translation, cultural adaptation, and validation of the Pain Beliefs and Perceptions Inventory (PBPI) for the European Portuguese language and chronic pain population. Methods: This is a longitudinal multicenter validation study. A Portuguese version of the PBPI (PBPI-P) was created through a process of translation, back translation, and expert panel evaluation. The PBPI-P was administered to a total of 122 patients from 13 chronic pain clinics in Portugal, at baseline and after 7 days. Internal consistency and test-retest reliability were assessed by Cronbach's alpha (α) and intraclass correlation coefficient (ICC). Construct (convergent and discriminant) validity was assessed based on a set of previously developed theoretical hypotheses about interrelations between the PBPI-P and other measures. Exploratory and confirmatory factor analyses were performed to test the theoretical structure of the PBPI-P. Results: The internal consistency and test-retest reliability coefficients for each respective subscale were α = 0.620 and ICC = 0.801 for mystery; α = 0.744 and ICC = 0.841 for permanence; α = 0.778 and ICC = 0.791 for constancy; and α = 0.764 and ICC = 0.881 for self-blame. Exploratory and confirmatory factor analysis revealed a four-factor structure (performance, constancy, self-blame, and mystery) that explained 63% of the variance. The construct validity of the PBPI-P was shown to be adequate, with more than 90% of the previously defined hypotheses regarding interrelations with other measures confirmed. Conclusion: The PBPI-P has been shown to be adequate and to have excellent reliability, internal consistency, and validity. It may contribute to a better pain assessment and is suitable for research and clinical use. info:eu-repo/semantics/publishedVersion

Objective Pain is a prominent feature of osteoarthritis (OA). To further understand the primary mechanisms of nociception in OA, we studied the expression of the phenotype markers calcitonin gene-related peptide (CGRP), isolectin B4 (IB4), and neurofilament 200 (NF200) in sensory neurons innervating the OA knee joint in rats. Methods OA was induced in rats by intraarticular injection of 2 mg of mono-iodoacetate (MIA) into the knee. Neurons innervating the joint were identified by retrograde labeling with fluorogold in dorsal root ganglia (DRG) and colocalized with neurochemical markers by immunofluorescence. The total number of DRG cells was determined by stereologic methods in Nissl-stained sections. Results A 37% decrease in the number of fluorogold-backlabeled cells was observed in rats with OA when compared with control rats, even though no decrease in the total number of cells was observed. However, an increase in the number of medium/large cell bodies and a decrease in the number of the smallest cells were observed, suggesting the occurrence of perikarya hypertrophy. The percentage of CGRP-positive cells increased significantly, predominantly in medium/large cells, suggesting the occurrence of a phenotypic switch. Colocalization of CGRP and NF200 revealed no significant changes in the percentage of double-labeled cells, but an increase in the number of medium/large double-labeled cells was observed. No differences in the expression of either IB4 or NF200 were observed in fluorogold-backlabeled cells. Conclusion These results indicate that MIA-induced OA causes an up-regulation of CGRP in different subpopulations of primary afferent neurons in DRG due to a phenotypic switch and/or cell hypertrophy which may be functionally relevant in terms of the onset of pain in this pathologic condition.

Modulation of nociceptive transmission at the brainstem involves several neurochemical systems. The precise location and specific characteristics of nociceptive neurons activated in each system was never reported. In thisstudy, the presence of GABA B , μ-opioid, and neurokinin-1 (NK-1) receptors in brainstem nociceptive neurons was investigated by double-immunocytochemical detection of each receptor and noxious-evoked induction of the c-fos proto-oncogene. Noxious cutaneous mechanical stimulation significantly increased the proportions of neurons double-labelled for Fos and GABA B receptors in several brainstem regions, namely, the reticular formation of the caudal ventrolateral medulla (VLMlat and VLMrf), lateral reticular nucleus, spinal trigeminal nucleus, pars caudalis (Sp 5 C), nucleus of the solitary tract, dorsal reticular nucleus, ventral reticular nucleus, raphe obscurus nucleus and dorsal parabrachial nucleus (DPB). For μ-opioid receptors, the proportions of double-labelled neurons in noxious-stimulated animals were higher than in controls only in the VLMlat, VLMrf, Sp 5 C, DPB and A 5 noradrenergic cell group. As for the NK-1 receptor, no significant differences were found between control and stimulated animals. According to these results, neurons expressing GABA B , μ-opioid and NK-1 receptors at several pain control centres of the brainstem are differentially involved in processing nociceptive mechanical input. The data provide the definition of new supraspinal targets for selective modulation of nociceptive neurons in order to define better strategies of pain control.

Metabotropic glutamate receptors (mGluR) have been shown to play a role in the modulation of acute and inflammatory pain. Additionally, we have recently detected time-dependent changes in the mRNA expression of several mGluR subtypes in thalamic nuclei of monoarthritic (MA) rats. In the present study, mGluR1, -3, -4, and -7 subtype mRNA expression was analyzed by in situ hybridization with radioactively labelled oligonucleotide probes in cerebral cortical regions of normal and MA rats at 2, 4, and 14 days of the disease. The mGluR1, -4, and -7 mRNAs were at background level in normal rats and did not change in MA animals. In contrast, mGluR3 mRNA expression was abundant in normal rats and was significantly increased in cortical areas of MA rats at all time points. Higher changes were detected bilaterally at 4 days, predominantly in layers IV/V, in the motor, primary, and secondary somatosensory cortices (average increases of 50-75%), but maximum rises occurred in the contralateral cingulate cortex (+138%). No changes were detected in the auditory cortex. The present data show an up-regulation of mGluR3 mRNA expression in the motor, somatosensory, and limbic cortices of MA rats. This possibly reflects the occurrence of central mechanisms counteracting the increased transmission of nociceptive input arising from the inflamed paw and the impaired motor behavior of these rats. Changes in the cingulate cortex may be related to the motivational-affective component of nociception.

Previous data have shown that noxious thermal stimulation of the hind leg in the anesthetized rat causes c-fos activation in the paraventricular nucleus of the hypothalamus (PVN); in other brain nuclei, including the cathecholaminergic cell groups of the caudal medulla; and in the adenohypophysis. Stimulation was followed by adrenocorticotropic hormone plasma release but did not provoke cardiovascular changes. In the current study, the afferent central pathways conveying the nociceptive input to the PVN were studied throughout the brain by using double labeling for the Fos-protein and the retrograde tracer cholera toxin subunit B (CTb) injected into the PVN. Although double labeling occurred in several hypothalamic nuclei, the periaqueductal gray, the lateral parabrachial area, and the catecholaminergic medullary groups, high rates of double labeling occurred only in the cells of the A1 region of the ventrolateral medulla (≈83% of CTb-labeled cells expressing c-fos). Further triple labeling with tyrosine hydroxylase (TH) revealed that > 80% of the double-labeled cells were TH-immunoreactive. The spinal cord had the usual strong c-fos expression but showed no retrograde labeling from the PVN. Noxious stimulation caused corticosterone plasma release. To ascertain a possible link of spinofugal neurons with the A1 cells, biotinylated dextran amine was injected into the spinal dorsal horn. Numerous anterogradely labeled fibers with bouton-like structures were observed, with the latter apposed to double- and triple-labeled cells in the A1 region. It is suggested that a dysynaptic route relayed in the A1 region conveys the nociceptive somatic input from the spinal cord to the PVN. Noxious stimulation may act as a systemic stressor, activating the hypothalamic-pituitary-adrenal axis. J. Comp. Neurol. 413:129–145, 1999. © 1999 Wiley-Liss, Inc.

Peripheral noxious stimulation evokes functional and biochemical changes in the spinal cord which results in central sensitization and hyperalgesia, but at the same time also induces the activation of inhibitory control systems. The purpose of the present study was to investigate whether the adaptive changes induced by ongoing peripheral inflammation influence the spinal cord expression of c-Fos (a commonly used marker of neuronal activity) following an additional acute noxious stimulus. Therefore, the spinal expression of c-Fos was immunohistochemically investigated following noxious thermal stimulation of a rat monoarthritic hindpaw at various time points (1, 4, 8, 21 days) after induction of monoarthritis. Compared to normal rats, c-Fos expression following ipsilateral noxious thermal stimulation of monoarthritic rats was strongly modified in the deep laminae of the dorsal horn depending on the time course of inflammation. At 1 day of monoarthritis, an enhanced ipsilateral expression (135% and 208% of normal rats in laminae III-VI and VII, respectively) and at 3 weeks a reduced expression (38% and 23% of normal rats in laminae III-VI and VII, respectively) was detected. The amount of c-Fos-positive neurons in the ipsilateral superficial laminae I and II was unchanged at all time points investigated. To assess excitability changes on the contralateral side at an early stage of inflammation, a group of monoarthritic rats received a contralateral noxious stimulus at day 1 of monoarthritis. This resulted in a potentiated expression of c-Fos ipsilateral to the acute noxious stimulus (i.e., contralateral to the monoarthritic hindpaw) restricted to lamina II (137% of normal rats) of the dorsal horn. The data showed that changes in c-Fos expression depended on the time point of noxious heat stimulation (NHS) of monoarthritic rats, and differed in the ipsi- and contralateral side of the spinal cord. In addition to a possible habituation of c-Fos expression, it may be speculated that the time course-dependent changes reflect laminae-specific modulations of excitatory and inhibitory mechanisms during monoarthritis. Further studies are necessary in order to provide more insights into the contribution of these mechanisms on noxious stimulus-evoked c-Fos expression.