Neuropathic pain is a clinical manifestation of nerve injury difficult to treat even with potent analgesic compounds. Here, we used different lines of genetically modified mice to clarify the role played by CB₂cannabinoid receptors in the regulation of the central immune responses leading to the development of neuropathic pain. CB₂knock-out mice and wild-type littermates were exposed to sciatic nerve injury, and both genotypes developed a similar hyperalgesia and allodynia in the ipsilateral paw. Most strikingly, knock-outs also developed a contralateral mirror image pain, associated with an enhanced microglial and astrocytic expression in the contralateral spinal horn. In agreement, hyperalgesia, allodynia, and microglial and astrocytic activation induced by sciatic nerve injury were attenuated in transgenic mice overexpressing CB₂receptors. These results demonstrate the crucial role of CB₂cannabinoid receptor in modulating glial activation in response to nerve injury. The enhanced manifestations of neuropathic pain were replicated in irradiated wild-type mice reconstituted with bone marrow cells from CB₂knock-outs, thus demonstrating the implication of the CB₂receptor expressed in hematopoietic cells in the development of neuropathic pain at the spinal cord.

Background: The first years of university can be very challenging for students. Previous research has focused on the study of the prevalence of burnout and of psychological distress in medical students. The aim of this study was to investigate the prevalence of psychological symptoms and burnout reported by first-year students, the relationship between these variables and their academic performance, and the differences between health and non-health sciences students. Methods: An observational study with a cross-sectional design was performed. Students of health sciences (medicine, nursing, physiotherapy, psychology), and non-health sciences (biology, social sciences, business management, and engineering) undergraduate programs completed the Brief Symptom Inventory (BSI-18) and the Maslach Burnout Inventory-Student Survey (MBI-SS). Students’ grades for the first semester were collected. Results: A sample of 506 students participated. Prevalence of psychological distress was 27.1% and burnout was 7.3%. Academic performance was unaffected in relation to either psychological distress or burnout. Non-health sciences students showed a greater risk of depression. Conclusions: This study provides evidence of the high prevalence of psychological distress in the first year of college. Even when burnout prevalence was low, the results suggest the need to introduce prevention programs to improve the psychological wellbeing of these students.

Epidemiological studies help to establish the health status in a country and allow a better allocation of economic resources. This survey estimated pain prevalence in Catalonia (Spain), analysed its relationship with demographic variables and evaluated pain-associated disabilities. The study was carried out in 1964 adults via phone interviews asking about any pain complaint they experienced in the last 6 months, regardless of its intensity and duration. Overall pain prevalence was 78.6%, significantly lower in men, with a trend to decrease with age. Back (50.9%), head (42%) and legs (36.8%) were the most affected locations. Less educated people reported, in general, higher prevalences. Pain described to be most annoying was related to musculoskeletal disease (26.2%) and migraines (16.5%). Pain was either very severe or unbearable in 33% of the sample, with women and older people reporting higher intensities. Personal and social activities were affected in 25.4% of cases and in 10.4% they became virtually impossible. Both the limitation of activity and the need for bed rest, which occurred in 19.6% of those who suffered pain, were more common amongst unemployed people, whereas 10.2% of workers had to take days off work due to pain, and 3.3% were fully incapacitated by it. In conclusion, the prevalence of pain was clearly higher among women, with an inverse relationship to age. Back pain and headaches were most prevalent and pain was rated as very severe to unbearable in one third of the patients. Pain-associated disabilities were a frequent finding. The present survey reports that pain is a substantial problem in the Catalonian population and generally reflects the characteristics of data previously reported in Anglo-saxon and Scandinavian countries.

The research of new therapeutic strategies for neuropathic pain represents a major current priority. Important drawbacks to advance in the development of these therapies are the limited translational value of the animal models now available and the elucidation of the complex neuronal and immune pathophysiological mechanisms underlying neuropathic pain. One of the neurotransmitter systems participating in neuropathic pain control that has recently raised a particular interest is the endocannabinoid system. This system is highly expressed in neurons and immune cells, and it plays a crucial role in the development of neuropathic pain. Preclinical studies have provided important findings, revealing the potential interest of the endocannabinoid system for the treatment of neuropathic pain. These studies have reported the analgesic effects of cannabinoid agonists in multiple neuropathic pain models, and they have identified specific targets within this system to develop more effective and safe analgesic compounds. However, further studies using more relevant neuropathic pain animal models are required to confirm these interesting results. Several clinical studies suggest that cannabinoids significantly reduced neuropathic pain, although most of these trials fail the required standards of quality. The different pain patient populations included in the systematic reviews also make it difficult to get adequate conclusions. Therefore, additional clinical trials that consider an adequate number of patients, the use active treatments as controls, and longer duration of administration are required to have an adequate profile of the effectiveness and safety of cannabinoids in neuropathic pain.

Nerve injuries often lead to neuropathic pain syndrome. The mechanisms contributing to this syndrome involve local inflammatory responses, activation of glia cells, and changes in the plasticity of neuronal nociceptive pathways. Cannabinoid CB₂receptors contribute to the local containment of neuropathic pain by modulating glial activation in response to nerve injury. Thus, neuropathic pain spreads in mice lacking CB₂receptors beyond the site of nerve injury. To further investigate the mechanisms leading to the enhanced manifestation of neuropathic pain, we have established expression profiles of spinal cord tissues from wild-type and CB₂-deficient mice after nerve injury. An enhanced interferon-γ (IFN-γ) response was revealed in the absence of CB₂signaling. Immunofluorescence stainings demonstrated an IFN-γ production by astrocytes and neurons ispilateral to the nerve injury in wild-type animals. In contrast, CB₂-deficient mice showed neuronal and astrocytic IFN-γ immunoreactivity also in the contralateral region, thus matching the pattern of nociceptive hypersensitivity in these animals. Experiments in BV-2 microglia cells revealed that transcriptional changes induced by IFN-γ in two key elements for neuropathic pain development, iNOS (inducible nitric oxide synthase) and CCR2, are modulated by CB₂receptor signaling. The most direct support for a functional involvement of IFN-γ as a mediator of CB₂signaling was obtained with a double knock-out mouse strain deficient in CB₂receptors and IFN-γ. These animals no longer show the enhanced manifestations of neuropathic pain observed in CB₂knock-outs. These data clearly demonstrate that the CB₂receptor-mediated control of neuropathic pain is IFN-γ dependent.