Neuropathic pain is a chronic pain caused by a disease or damage to the somatosensory nervous system. The knowledge about the complete mechanisms is incomplete, but the role of oxidative compounds has been evaluated. In this context, we highlight the transient potential receptor vanilloid 4 (TRPV4), a non-selective cation channel, that can be activated by oxidated compounds. In clinical trials, the TRPV4 antagonist (GSK2798745) has been well-tolerated in healthy volunteers. The TRPV4 activation by oxidative compounds, such as hydrogen peroxide (H₂O₂) and nitric oxide (NO), has been researched in neuropathic pain models. Thus, the modulation of TRPV4 activation by decreasing oxidated compounds could represent a new pharmacological approach for neuropathic pain treatment. Most models evaluated the TRPV4 using knockout mice, antagonist or antisense treatments and detected mechanical allodynia, hyposmotic solution-induced nociception and heat hyperalgesia, but this channel is not involved in cold allodynia. Only H₂O₂ and NO were evaluated as TRPV4 agonists, so one possible target to reduce neuropathic pain should focus on reducing these compounds. Therefore, this review outlines how the TRPV4 channel represents an innovative target to tackle neuropathic pain signaling in models induced by trauma, surgery, chemotherapy, cancer, diabetes and alcohol intake.

Despite the unique and complex nature of cancer pain, the activation of different ion channels can be related to the initiation and maintenance of pain. The transient receptor potential vanilloid 4 (TRPV4) is a cation channel broadly expressed in sensory afferent neurons. This channel is activated by multiple stimuli to mediate pain perception associated with inflammatory and neuropathic pain. Here, we focused on summarizing the role of TRPV4 in cancer etiology and cancer-induced pain mechanisms. Many studies revealed that the administration of a TRPV4 antagonist and TRPV4 knockdown diminishes nociception in chemotherapy-induced peripheral neuropathy (CIPN). Although the evidence on TRPV4 channels’ involvement in cancer pain is scarce, the expression of these receptors was reportedly enhanced in cancer-induced bone pain (CIBP), perineural, and orofacial cancer models following the inoculation of tumor cells to the bone marrow cavity, sciatic nerve, and tongue, respectively. Effective pain management is a continuous problem for patients diagnosed with cancer, and current guidelines fail to address a mechanism-based treatment. Therefore, examining new molecules with potential antinociceptive properties targeting TRPV4 modulation would be interesting. Identifying such agents could lead to the development of treatment strategies with improved pain-relieving effects and fewer adverse effects than the currently available analgesics.

Maclura tinctoria is a tree species native from Brazil and rich in phenolic compounds. Since plant antibacterial activity is highly associated with phenolic compound concentration, we aim to evaluate the in vitro antimicrobial activity of different extracts against fish pathogenic bacteria. In addition, some phenolic compounds have central depressant effects and can be useful in aquaculture due to possible sedative and/or anesthetic effects. Four M. tinctoria extracts were extracted separately with ethanol; leaves (LE), bark (BE), heartwood (HE), and the sapwood (SE). In vitro antimicrobial activity was tested against Aeromonas strains at concentrations of 6400 to 3.125 μg/mL. The sedative effect was evaluated for 24 h with 30 and 100 mg/L concentrations. Chemical composition was analyzed by HPLC-DAD-MS. The HE extract had the best MIC (400 µg/mL) and MBC (800 µg/mL) compared to the LE, BE, and SE extracts. LE extract induced deep sedation and the BE, SE, and HE extracts induced light sedation. Additionally, BE, SE, and HE induced a normal behavior without side effects. Polyphenolic compounds with antimicrobial activity and sedative effects were identified mainly in HE. Thus, HE extract is safe and can be used as a sedative for silver catfish.