Browse by Audience
Opioid use is well-documented in several countries: some countries struggle with overuse while others have almost no access to opioids. For Europe, limited data are available. This study analysed Hungarian opioid utilisation in ambulatory care between 2006 and 2020.
Learn More >The COVID-19 pandemic transformed everyday life, but the implications were most impactful for vulnerable populations, including patients with chronic pain. Moreover, persistent pain is increasingly recognised as a key manifestation of long COVID. This narrative review explores the consequences of the COVID-19 pandemic for chronic pain. Publications were identified related to the COVID-19 pandemic influence on the burden of chronic pain, development of new-onset pain because of long COVID with proposed mechanisms and COVID-19 vaccines and pain interventions. Broadly, mechanisms underlying pain due to SARS-CoV-2 infection could be caused by 'systemic inflammatory-immune mechanisms', 'direct neuropathic mechanisms' or 'secondary mechanisms due to the viral infection or treatment'. Existing chronic pain populations were variably impacted and social determinants of health appeared to influence the degree of effect. SARS-CoV-2 infection increased the absolute numbers of patients with pain and headache. In the acute phase, headache as a presenting symptom predicted a milder course. New-onset chronic pain was reportedly common and likely involves multiple mechanisms; however, its prevalence decreases over time and symptoms appear to fluctuate. Patients requiring intensive support were particularly susceptible to long COVID symptoms. Some evidence suggests steroid exposure (often used for pain interventions) may affect vaccine efficacy, but there is no evidence of clinical repercussions to date. Although existing chronic pain management could help with symptomatic relief, there is a need to advance research focusing on mechanism-based treatments within the domain of multidisciplinary care.
Learn More >Burn injuries are among the highly prevalent medical conditions worldwide that occur mainly in children, military veterans and victims of fire accidents. It is one of the leading causes of temporary as well as permanent disabilities in patients. Burn injuries are accompanied by pain that persists even after recovery from tissue damage which puts immense pressure on the healthcare system. The pathophysiology of burn pain is poorly understood due to its complex nature and lack of considerable preclinical and clinical shreds of evidence, that creates a substantial barrier to the development of new analgesics. Burns damage the skin layers supplied with nociceptors such as NAV1.7, TRPV1, and TRPA1. Burn injury-mediated co-localization and simultaneous activation of TRPA1 and TRPV1 in nociceptive primary afferent C-fibers which contributes to the development and maintenance of chronic pain. Burn injuries are accompanied by central sensitization, a key feature of pain pathophysiology mainly driven by a series of cascades involving aberrations in the glutamatergic system, microglial activation, release of neuropeptides, cytokines, and chemokines. Activation of p38 mitogen-activated protein kinase, altered endogenous opioid signaling, and distorted genomic expression are other pathophysiological factors responsible for the development and maintenance of burn pain. Here we discuss comprehensive literature on molecular mechanisms of burn pain and potential targets that could be translated into near future therapeutics.
Learn More >Anti-CGRP monoclonal antibodies (CGRPmAbs) enlarged migraine prevention options. They work targetedly, safely, and efficiently in many patients. Inexplicably, a proportion of patients show scarce improvement.
Learn More >Tumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2) possesses potent anti-inflammatory effect. However, if TIPE2 ameliorates sciatic nerve injury (SNI)-induced inflammation and pain remains undiscussed, and the underlying role TAK1 in it were unknown. To verify our imagine, we performed SNI surgery, and analyzed expression and colocalization of TIPE2 and TAK1 in spinal cord and dorsal root neurons (DRG) by immunofluorescence staining and western blot. And the biological analysis, inflammatory factors, and pathological improvement were determined, and the regulation of TIPE2 in TAK1, phosphor-NF-κB, phospho-JNK was also tested by immunofluorescence staining and western blot. Experimental results showed the parabola-like change of TIPE2 and rising expression of TAK1 in spinal cord and DRG. And intrathecal TIPE2 injection could significantly improve the status of SNI rats, inhibit level of IL-6, IL-10 and TNF-α, raise the thermal withdrawal relax latency and mechanical withdrawal thresholds. Meanwhile, we also detected how TIPE2 regulated TAK1, and the downstream pathway NF-κB and JNK. The result indicated that TIPE2 could reduce TAK1 expression, and make NF-κB and JNK inactivated. To deeply discuss the potential mechanism, we injected TAK1 oligodeoxynucleotide into rats, and found that TIPE2 exerted the protective role against SNI through TAK1. In brief, TIPE2 reduced expression of TAK1, thereby inhibiting activation of NF-kB and JNK, further improving the neuroinflammation and neuropathic pain. TIPE2 played a protective role in sciatic nerve injury rats through regulating TAK1.
Learn More >Chronic pain trials commonly allow auxiliary pain medications such as rescue and concomitant analgesics in addition to the randomized treatment. Changes in auxiliary pain medications after randomization represent intercurrent events that may affect either the interpretation or the existence of the measurements associated with the clinical question of interest, complicating the assessment of treatment efficacy. In chronic pain trials, pain intensity typically varies and patients may take the auxiliary medications 1 day but not the next or increase and decrease the dosages temporarily while continuing their randomized study medication. This distinctive feature of auxiliary pain medications as an intercurrent event has received little attention in the literature. Further clarifications on how to manage these issues are therefore pressing. Here we provide perspectives on issues related to auxiliary pain medication-related intercurrent events in randomized controlled chronic pain trials considering the strategies suggested in the E9(R1) addendum to the ICH guideline on statistical principles for clinical trials.
Learn More >The pathogenesis of migraine, as well as cluster headache (CH), is yet a debated question. In this review, we discuss the possible role of tyrosine and tryptophan metabolism in the pathogenesis of primary headaches, including the abnormalities in the synthesis of neurotransmitters. High level of dopamine, low level of norepinephrine, and very elevated levels of octopamine and synephrine were found in the plasma of episodic migraine without aura. We hypothesize that the imbalance between the levels of neurotransmitters and elusive amines synthesis is due to a metabolic shift directing tyrosine toward increased decarboxylase and reduced hydroxylase enzyme activities, favored by a state of neuronal hyperexcitability and a reduced mitochondrial activity. In addition, we present biochemical studies performed in chronic migraine (CM) and chronic tension-type headache patients (CTTH) to verify if the same anomalies are present in these primary headaches and, if so, their possible role in the chronicity process of CM and CTTH. The results show that important abnormalities of tyrosine-related metabolites are present only in CM patients while tryptamine plasma levels were found significantly lower in both CM and CTTH patients. Because of this, we propose that migraine and, possibly, CH attacks derive from neurotransmitter and neuromodulator metabolic abnormalities in a hyperexcitable and hypoenergetic brain that spread from the frontal lobe, downstream, resulting in abnormally activated nuclei of the pain matrix. The low tryptamine plasma levels found in CM and CTTH patients suggest that these two primary chronic headaches are characterized by a common insufficient serotoninergic control of the pain threshold.
Learn More >Peripheral and central nociceptive sensitization is a critical pathogenetic component in osteoarthritis (OA) chronic pain. T-type calcium channel 3.2 (Ca3.2) regulates neuronal excitability and plays important roles in pain processing. We previously identified that enhanced T-type/Ca3.2 activity in the primary sensory neurons (PSNs) of dorsal root ganglia (DRG) is associated with neuropathic pain behavior in a rat model of monosodium iodoacetate (MIA)-induced knee OA. PSN-specific T-type/Ca3.2 may therefore represent an important mediator in OA painful neuropathy. Here, we test the hypothesis that the T-type/Ca3.2 channels in PSNs can be rationally targeted for pain relief in MIA-OA.
Learn More >