Background: Acute treatment with the selective serotonin reuptake inhibitor (SSRI), fluoxetine (Flx), induces anxiety-like behavioral effects. The serotonin 2A receptor (5-HT 2A ) is implicated in the modulation of anxiety-like behavior, however its contribution to the anxiogenic effects of acute Flx remains unclear. Here, we examined the role of the 5-HT 2A receptor in the effects of acute Flx on anxiety-like behavior, serum corticosterone levels, neural activation and immediate early gene (IEG) expression in stress-responsive brain regions, using 5-HT 2A receptor knockout (5-HT 2A −/− ) mice of both sexes. Methods: 5-HT 2A −/− and wild-type (WT) male and female mice received a single administration of Flx or vehicle, and were examined for anxiety-like behavior, serum corticosterone levels, FBJ murine osteosarcoma viral oncogene homolog peptide (c-Fos) positive cell numbers in stress-responsive brain regions of the hypothalamus and prefrontal cortex (PFC), and PFC IEG expression. Results: The increased anxiety-like behavior and enhanced corticosterone levels evoked by acute Flx were unaltered in 5-HT 2A −/− mice of both sexes. 5-HT 2A −/− female mice exhibited a diminished neural activation in the hypothalamus in response to acute Flx. Further, 5-HT 2A −/− male, but not female, mice displayed altered baseline expression of several IEGs (brain-derived neurotrophic factor ( Bdnf ), Egr2, Egr4 , FBJ osteosarcoma gene ( Fos ), FBJ murine osteosarcoma viral oncogene homolog B ( Fosb ), Fos-like antigen 2 ( Fosl2 ), Homer scaffolding protein ( Homer ) 1-3 ( Homer1-3 ), Jun proto-oncogene ( Jun )) in the PFC. Conclusion: Our results indicate that the increased anxiety and serum corticosterone levels evoked by acute Flx are not influenced by 5-HT 2A receptor deficiency. However, the loss of function of the 5-HT 2A receptor alters the degree of neural activation of the paraventricular nucleus (PVN) of the hypothalamus in response to acute Flx, and baseline expression of several IEGs in the PFC in a sexually dimorphic manner.

Challenges in the management of ocular pain are an underappreciated topic. Currently available therapeutics lack both efficacy and clear guidelines for their use, with many also possessing unacceptable side effects. Promising novel agents would offer analgesic, anti-inflammatory, and possibly neuroprotective actions; have favorable ocular safety profiles; and show potential in managing neuropathic pain. Growing evidence supports a link between the endocannabinoid system (ECS) and a range of physiological and disease processes, notably those involving inflammation and pain. Both preclinical and clinical data suggest analgesic and anti-inflammatory actions of cannabinoids and ECS-modifying drugs in chronic pain conditions, including those of neuropathic origin. This review will examine existing evidence for the anatomical and physiological basis of ocular pain, specifically, ocular surface disease and the development of chronic ocular pain. The mechanism of action, efficacy, and limitations of currently available treatments will be discussed, and current knowledge related to ECS-modulation of ocular pain and inflammatory disease will be summarized. A perspective will be provided on the future directions of ECS research in terms of developing cannabinoid therapeutics for ocular pain.

Botulinum toxin is one of the most potent molecule known to mankind. A neurotoxin, with high affinity for cholinergic synapse, is effectively capable of inhibiting the release of acetylcholine. On the other hand, botulinum toxin is therapeutically used for several musculoskeletal disorders. Although most of the therapeutic effect of botulinum toxin is due to temporary skeletal muscle relaxation (mainly due to inhibition of the acetylcholine release), other effects on the nervous system are also investigated. One of the therapeutically investigated areas of the botulinum neurotoxin (BoNT) is the treatment of pain. At present, it is used for several chronic pain diseases, such as myofascial syndrome, headaches, arthritis, and neuropathic pain. Although the effect of botulinum toxin in pain is mainly due to its effect on cholinergic transmission in the somatic and autonomic nervous systems, research suggests that botulinum toxin can also provide benefits related to effects on cholinergic control of cholinergic nociceptive and antinociceptive systems. Furthermore, evidence suggests that botulinum toxin can also affect central nervous system (CNS). In summary, botulinum toxin holds great potential for pain treatments. It may be also useful for the pain treatments where other methods are ineffective with no side effect(s). Further studies will establish the exact analgesic mechanisms, efficacy, and complication of botulinum toxin in chronic pain disorders, and to some extent acute pain disorders.

The opioid receptors are a family of G-protein coupled receptors (GPCRs) with close structural homology. The opioid receptors are activated by a variety of endogenous opioid neuropeptides, principally β-endorphin, dynorphins, leu- and met-enkephalins. The clinical potential of targeting opioid receptors has largely focused on the development of analgesics. However, more recent attention has turned to the role of central opioid receptors in the regulation of stress responses, anhedonia and mood. Activation of the κ opioid receptor (KOP) subtype has been shown in both human and rodent studies to produce dysphoric and pro-depressive like effects. This has led to the idea that selective KOP antagonists might have therapeutic potential as antidepressants. Here we review data showing that mixed μ opioid (MOP) and KOP antagonists have antidepressant-like effects in rodent behavioural paradigms and highlight comparable studies in treatment-resistant depressed patients. We propose that developing multifunctional ligands which target multiple opioid receptors open up the potential for fine-tuning hedonic responses mediated by opioids. This alternative approach towards targeting multiple opioid receptors may lead to more effective treatments for depression.