Browse by Audience
Adults with persistent pain frequently report cannabis use to help manage their symptoms. The impact of cannabis use on cognition in the presence of concurrent symptoms of depression and anxiety is poorly understood.
Learn More >Fabry disease (FD) is an X-linked lysosomal storage disorder that leads to cellular globotriaosylceramide (Gb3) accumulation due to mutations in the gene encoding α-galactosidase A. Trigger-induced acral burning pain is an early FD symptom of unknown pathophysiology. We aimed at investigating the potential role of skin fibroblasts in nociceptor sensitization.
Learn More >Evidence-based severity assessment is essential as a basis for ethical evaluation in animal experimentation to ensure animal welfare, legal compliance and scientific quality. To fulfil these tasks scientists, animal care and veterinary personnel need assessment tools that provide species-relevant measurements of the animals' physical and affective state. In a three-centre study inter-laboratory robustness of body weight monitoring, mouse grimace scale (MGS) and burrowing test were evaluated. The parameters were assessed in naïve and tramadol treated female C57BL/6J mice. During tramadol treatment a body weight loss followed by an increase, when treatment was terminated, was observed in all laboratories. Tramadol treatment did not affect the MGS or burrowing performance. Results were qualitatively comparable between the laboratories, but quantitatively significantly different (inter-laboratory analysis). Burrowing behaviour seems to be highly sensitive to inter-laboratory differences in testing protocol. All locations obtained comparable information regarding the qualitative effect of tramadol treatment in C57BL/6J mice, however, datasets differed as a result of differences in test and housing conditions. In conclusion, our study confirms that results of behavioural testing can be affected by many factors and may differ between laboratories. Nevertheless, the evaluated parameters appeared relatively robust even when conditions were not harmonized extensively and present useful tools for severity assessment. However, analgesia-related side effects on parameters have to be considered carefully.
Learn More >Animal models reveal that deafferenting forelimb injuries precipitate reorganization in both contralateral and ipsilateral somatosensory cortices. The functional significance and duration of these effects are unknown, and it is unclear whether they also occur in injured humans. We delivered cutaneous stimulation during functional magnetic resonance imaging (fMRI) to map the sensory cortical representation of the intact hand and lower face in a group of chronic, unilateral, upper extremity amputees (N = 19) and healthy matched controls (N = 29). Amputees exhibited greater activity than controls within the deafferented former sensory hand territory (S1f) during stimulation of the intact hand, but not of the lower face. Despite this cortical reorganization, amputees did not differ from controls in tactile acuity on their intact hands. S1f responses during hand stimulation were unrelated to tactile acuity, pain, prosthesis usage, or time since amputation. These effects appeared specific to the deafferented somatosensory modality, as fMRI visual mapping paradigm failed to detect any differences between groups. We conclude that S1f becomes responsive to cutaneous stimulation of the intact hand of amputees, and that this modality-specific reorganizational change persists for many years, if not indefinitely. The functional relevance of these changes, if any, remains unknown.
Learn More >To evaluate measurement and associations between pain severity and opioid craving in individuals with chronic pain on long-term opioid therapy and/or with opioid use disorder.
Learn More >To present the clinical picture, the associated complications and the genetic findings of Jordanian patients diagnosed with Congenital insensitivity to pain with anhidrosis (CIPA).
Learn More >Metformin, an adenosine monophosphate (AMP)-activated protein kinase activator, as well as a common drug for type 2 diabetes, has previously been shown to decrease mechanical allodynia in mice with neuropathic pain. The objective of this study is to determine if treatment with metformin during the first 3 weeks after fracture would produce a long-term decrease in mechanical allodynia and improve a complex behavioral task (burrowing) in a mouse tibia fracture model with signs of complex regional pain syndrome.
Learn More >Neuropathic pain caused by nerve injury presents with severe spontaneous pain and a variety of comorbidities, including deficits in higher executive functions. None of these clinical problems are adequately treated with current analgesics. Targeting of the mitogen-activated protein kinase-interacting kinase (MNK1/2) and its phosphorylation target, the mRNA cap binding protein eIF4E, attenuates many types of nociceptive plasticity induced by inflammatory mediators and chemotherapeutic drugs but inhibiting this pathway does not alter nerve injury-induced mechanical allodynia. We used genetic manipulations and pharmacology to inhibit MNK-eIF4E activity in animals with spared nerve injury, a model of peripheral nerve injury (PNI)-induced neuropathic pain. We assessed the presence of spontaneous pain using conditioned place preference. We also tested performance in a medial prefrontal cortex (mPFC)-dependent rule-shifting task. WT neuropathic animals showed signs of spontaneous pain and were significantly impaired in the rule-shifting task while genetic and pharmacological inhibition of the MNK-eIF4E signaling axis protected against and reversed spontaneous pain and PNI-mediated cognitive impairment. Additionally, pharmacological and genetic inhibition of MNK-eIF4E signaling completely blocked and reversed maladaptive shortening in the length of axon initial segments (AIS) in the mPFC of PNI mice. Surprisingly, these striking positive outcomes on neuropathic pain occurred in the absence of any effect on mechanical allodynia, a standard test for neuropathic pain efficacy. Our results illustrate new testing paradigms for determining preclinical neuropathic pain efficacy and point to the MNK inhibitor tomivosertib (eFT508) as an important drug candidate for neuropathic pain treatment.
Learn More >Chronic pain is a cause of morbidity, interference with daily functioning, decreased health and quality of life. Purpose in life acts as a protective factor and mitigates these consequences. This cross-sectional study aimed to determine whether purpose in life contributed to psychological morbidity and quality of life in patients with chronic pain by controlling psychological variables related to health (pain severity and interference, pain perceptions, pain catastrophizing and coping). The sample included 103 patients diagnosed with chronic pain. Results showed that purpose in life independently contributed to psychological morbidity and to mental quality of life, but not to physical quality of life, after controlling for pain-related variables. Results showed the relevance of purpose in life to identify patients at risk of developing psychological morbidity and decreased quality of life, suggestting the need to intervene in chronic pain, specifically on purpose in life, to prevent psychological morbidity and promote quality of life, in this population.
Learn More >The chronic constriction injury (CCI) of the sciatic nerve is a nerve injury-based model of neuropathic pain (NP). Comorbidities of NP such as depression, anxiety, and cognitive deficits are associated with a functional reorganization of the medial prefrontal cortex (mPFC). Here, we have employed an adapted model of CCI by placing one single loose ligature around the sciatic nerve in mice for investigating the alterations in sensory, motor, affective, and cognitive behavior and in electrophysiological and biochemical properties in the prelimbic division (PrL) of the mPFC. Our adapted model of CCI induced mechanical allodynia, motor, and cognitive impairments and anxiety- and depression-like behavior. In the PrL division of mPFC was observed an increase in GABA and a decrease in d-aspartate levels. Moreover an increase in the activity of neurons responding to mechanical stimulation with an excitation, mPFC (+), and a decrease in those responding with an inhibition, mPFC (-), was found. Altogether these findings demonstrate that a single ligature around the sciatic nerve was able to induce sensory, affective, cognitive, biochemical, and functional alterations already observed in other neuropathic pain models and it may be an appropriate and easily reproducible model for studying neuropathic pain mechanisms and treatments.
Learn More >