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Trigeminal neuropathic pain has been modeled in rodents through the constriction of the infraorbital nerve (CCI-ION). Sensory alterations, including spontaneous pain, and thermal and mechanical hyperalgesia are well characterized, but there is a notable lack of evidence about the affective pain component in this model. Evaluation of the emotional component of pain in rats has been proposed as a way to optimize potential translational value of non-clinical studies. In rats, 22 and 50 kHz ultrasonic vocalizations (USVs) are considered well-established measures of negative and positive emotional states, respectively. Thus, this study tested the hypothesis that trigeminal neuropathic pain would result, in addition to the sensory alterations, in a decrease of 50 kHz USV, which may be related to altered function of brain areas involved in emotional pain processing. CCI-ION surgery was performed on 60-day-old male Wistar rats. 15 days after surgery, von Frey filaments were applied to detect mechanical hyperalgesia, and USV was recorded. At the same timepoint, systemic treatment with d,l-amphetamine (1 mg/kg) allowed investigation of the involvement of the dopaminergic system in USV emission. Finally, brain tissue was collected to assess the change in tyrosine hydroxylase (TH) expression in the nucleus accumbens (NAc) and c-Fos expression in brain areas involved in emotional pain processing, including the prefrontal cortex (PFC), amygdala, and NAc. The results showed that CCI-ION rats presented mechanical hyperalgesia and a significant reduction of environmental-induced 50 kHz USV. Amphetamine caused a marked increase in 50 kHz USV emission in CCI-ION rats. In addition, TH expression was lower in constricted animals and c-Fos analysis revealed an increase in neuronal activation. Taken together, these data indicate that CCI-ION causes a reduction in the emission of environmental-induced appetitive calls concomitantly with facial mechanical hyperalgesia and that both changes may be related to a reduction in the mesolimbic dopaminergic activity.
Learn More >Substance P (SP) and calcitonin gene-related peptide (CGRP) have both been considered potential drug candidates in migraine therapy. In recent years, CGRP receptor inhibition has been established as an effective treatment, in particular as a prophylactic for chronic migraine. Curiously, inhibition of neurokinin receptor 1 (NK1R) failed to alleviate acute migraine attacks in clinical trials, and the neurokinins were consequently abandoned as potential antimigraine candidates. The reason behind this has remained enigmatic.Utilizing immunohistochemistry and semi-quantitative cell counts the expression of neurokinins and their associated receptors was examined in the rat trigeminal ganglion.Immunohistochemistry results revealed SP co-localization in CGRP positive neurons and C-fibres, where it mainly concentrated at boutons. Neurokinin A (NKA) was observed in a population of C-fibres and small neurons where it could co-localize with SP. In contrast, neurokinin B (NKB) did not co-localize with SP and was observed in large/medium sized neurons and Aδ-fibres. All neurokinin receptors (NK1-3R) were found to be expressed in a majority of trigeminal ganglion neurons and A-fibres.The functional release of SP and CGRP in the trigeminovascular system was stimulated with either 60 mM K+ or 100 nM capsaicin and measured with an enzyme-linked immunosorbent assay (ELISA). ELISA results established that SP can be released locally from trigeminovascular system. The released SP was comparatively minor compared to the CGRP release from stimulated dura mater, trigeminal ganglion neurons and fibres. We hypothesize that SP and CGRP signalling pathways may work in tandem to exacerbate painful stimuli in the TGV system.
Learn More >To investigate the efficacy, acceptability, and safety of muscle relaxants for low back pain.
Learn More >Mast cell (MC) activation could establish a positive feedback loop that perpetuates inflammation and maintains pain. Stabilizing MCs with ketotifen fumarate (KF) may disrupt this loop and relieve pain.
Learn More >Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease. Chronic pain is experienced by the vast majority of patients living with Parkinson's disease. The degeneration of dopaminergic neuron acts as the essential mechanism of Parkinson's disease in the midbrain dopaminergic pathway. The impairment of dopaminergic neurons leads to dysfunctions of the nociceptive system. Key cortical areas, such as the anterior cingulate cortex (ACC) and insular cortex (IC) that receive the dopaminergic projections are involved in pain transmission. Dopamine changes synaptic transmission via several pathway, for example the D2-adenly cyclase (AC)-cyclic AMP (cAMP)-protein kinase A (PKA) pathway and D1-G protein-coupled receptor kinase 2 (GRK2)-fragile X mental retardation protein (FMRP) pathway. The management of Parkinson's disease-related pain implicates maintenance of stable level of dopaminergic drugs and analgesics, however a more selective drug targeting at key molecules in Parkinson's disease-related pain remains to be investigated.
Learn More >The COVID-19 outbreak has been a great challenge in the management of chronic pain patients. We have conducted a rapid scoping review to assess the impact of the pandemic (and the associated public health measures) on the health status and management practices of chronic pain patients in Spain. To this end, we performed a bibliographic search in LitCOVID and PubMed, and reviewed official websites and documents, and expert reports. The review showed that (1) the studies consistently indicate that the pandemic has had a very negative impact on the physical and psychological health of chronic pain patients; (2) there are scarce data on how the pandemic affected pain unit consultations and a lack of protocols to organize health care in the face of future waves of contagion, with little implementation of telehealth. We make proposals to improve management of chronic pain patients in pandemic situations, which should pivot around 3 axes: (1) a coordinated response of all the relevant stakeholders to define a future roadmap and research priorities, (2) a biopsychosocial approach in pain management, and (3) development and implementation of novel telemedicine solutions.
Learn More >Pain is a common symptom accompanying the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Nonspecific discomfort such as sore throat and body ache are frequent. Parainfectious pain such as headache, myalgia, or neuropathic pain has also been reported. The latter seems to be associated with an autoimmune response or an affection of the peripheral neuromuscular system or the central nervous system because of the viral infection. Furthermore, chronic pain can be a complication of intensive care unit treatment due to COVID-19 itself (such as intensive care-acquired weakness) or of secondary diseases associated with the SARS-CoV-2 infection, including Guillain-Barré syndrome, polyneuritis, critical illness polyneuropathy, or central pain following cerebrovascular events. Data on long-lasting painful symptoms after clinically manifest COVID-19 and their consequences are lacking. In addition, preexisting chronic pain may be exacerbated by limited and disrupted health care and the psychological burden of the COVID-19 pandemic. Medical providers should be vigilant on pain during and after COVID-19.
Learn More >Patient beliefs about pain and opioids have been reported from qualitative data. To overcome limitations of unstructured assessments and small sample sizes, we determined if pain and pain medication beliefs varied by chronic pain status and opioid analgesic use (OAU) duration in primary care patients.
Learn More >Regular physical activity/exercise is an effective nonpharmacological treatment for individuals with chronic pain. Central inhibitory mechanisms, involving serotonin and opioids, are critical to analgesia produced by regular physical activity. The rostral ventromedial medulla (RVM) sends projections to the spinal cord to inhibit or facilitate nociceptive neurons and plays a key role in exercise-induced analgesia.
Learn More >Complex regional pain syndrome (CRPS) is a neuropathic pain condition of unknown etiology. Little is known of long-term outcomes of young adults who were diagnosed with CRPS as children.
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