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Depression and anxiety commonly occur in chronic pain states and the coexistence of these diseases worsens outcomes for both disorders and may reduce treatment adherence and response. Despite the advances in the knowledge of chronic pain mechanisms, pharmacological treatment is still unsatisfactory. Research based on exposure to environmental enrichment is currently under investigation and seems to offer a promising low‐cost strategy with no side effects. In this review, we discuss the role of inflammation as a major biological substrate and aetiological factor of chronic pain and depression/anxiety and report a collection of preclinical evidence of the effects and mechanisms of environmental enrichment. As microglia participates in the development of both conditions, we also discuss microglia as a potential target underlying the beneficial actions of environmental enrichment in chronic pain and comorbid depression/anxiety. We also discuss how alternative interventions under clinical guidelines, such as environmental enrichment, may improve treatment compliance and patient outcomes. LINKED ARTICLES This article is part of a themed issue on Building Bridges in Neuropharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.8/issuetoc

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There are a great number of studies about Brazilian scorpions. However, little is known about the venom of scorpions of northern Brazil, mainly about Tityus obscurus, which is responsible for the most number of accidents in the Amazon. Thus, this study aimed to evaluate some pharmacological effects of T. obscurus venom in rats and mice. In rats, the venom (10 mg/kg i.p.) caused hemorrhagic patches in the lung parenchyma but did not lead to pulmonary edema. There was a decrease in general activity, observed in the activity box after venom injection. The venom did not induce changes in the occurrence and intensity of experimentally induced convulsions, nor did it cause hippocampal neuronal loss. In mice, the LD obtained was 3.13 mg/kg (i.p.). Different doses of the venom (0.2; 1; 5; 10; 15 μg/30 μL per hind paw) induced edematogenic and moderate nociceptive activity in mice. The Tiyus serrulatus venom used as comparison caused more intense symptomatology in mice. Comparing to the venom of other Tityus scorpions of medical importance, that have convulsant and intense nociceptive effects and cause lung edema, as described in the literature, we can conclude that the venom of T. obscurus probably has different characteristics.

Polycystins (PKD2, PKD2L1, and PKD2L2) are members of the transient receptor potential family, which form ciliary ion channels. Most notably, PKD2 dysregulation in the kidney nephron cilia is associated with polycystic kidney disease, but the function of PKD2L1 in neurons is undefined. In this report, we develop animal models to track the expression and subcellular localization of PKD2L1 in the brain. We discover that PKD2L1 localizes and functions as a Ca 2+ channel in the primary cilia of hippocampal neurons that apically radiate from the soma. Loss of PKD2L1 expression ablates primary ciliary maturation and attenuates neuronal high-frequency excitability, which precipitates seizure susceptibility and autism spectrum disorder–like behavior in mice. The disproportionate impairment of interneuron excitability suggests that circuit disinhibition underlies the neurophenotypic features of these mice. Our results identify PKD2L1 channels as regulators of hippocampal excitability and the neuronal primary cilia as organelle mediators of brain electrical signaling.

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