Ahmed Olalekan Bakare

The role of T cells in chemotherapy-induced peripheral neuropathy (CIPN) is complex and shaped by biological and experimental factors, including sex, hormonal status, genetic background, and cancer model. This complexity has contributed to inconsistent findings among studies, limiting therapeutic progress. In this study, we investigate how T cells contribute to painful paclitaxel (PTX)-induced peripheral neuropathy (PIPN). Adult male T cell-competent (RNU ^+/− ) and T cell-deficient (RNU ^−/− ) rats were subcutaneously inoculated with tumor cells and subsequently treated with intraperitoneal PTX (8 mg/kg total dose). Reflexive (mechanical, heat, cold) and non-reflexive (burrowing, gait) pain behaviors were assessed from baseline through week 6. Immunohistochemistry (CD68, CX3CR1, CD206) and flow cytometry (CD163, CD86, CD11b/c, CD3, CD161a, CD45RA) were used to assess macrophage and lymphocyte populations. T cell-competent, but not -deficient, rats developed and maintained cold hypersensitivity following PTX. T cells also reduced the onset intensity of PTX-induced mechanical hypersensitivity. In T cell-competent rats, PTX reduced T and B cell counts and increased the CD4+/CD8+ T cell ratio across DRG, sciatic nerve, and spleen. PTX shifted macrophage polarization toward the M1 phenotype and reduced the M2/M1 ratio, independent of T cells. However, M2 macrophages (M2γ and M2a) increased specifically in the sciatic nerves of T cell-deficient rats. Additionally, natural killer (NK) cells decreased in PTX-treated, T cell-deficient rats but remained unchanged in T cell-competent rats. These findings highlight the complex role of T cells in PIPN. In PIPN, T cells play a critical role in driving PTX-induced cold hypersensitivity. A decrease in their number worsens pain intensity, possibly by altering the CD4+/CD8+ T cell balance. In contrast, NK cell reductions in T cell-deficient rats may contribute to hypersensitivity in the absence of T cells.

Asthma, a chronic inflammatory airway disease, leads to airflow obstruction and exhibits sex differences in prevalence and severity. Immunomodulatory diets, such as the ketogenic diet (high fat, low carbohydrate, moderate protein), may offer complementary benefits in managing airway inflammation. While anti-inflammatory effects of ketogenic diets are documented in cardiovascular diseases, their impact on asthma, especially regarding sex-specific differences, remains unexplored. Few studies on diet and asthma have considered sex as a biological factor. To test the hypothesis that a ketogenic diet affects airway inflammation in a sex-specific manner, we used a mouse allergic airway inflammation model. Male and female C57BL/6J mice (3–4 weeks old, n = 5–6/group) were fed a ketogenic diet or normal chow for 12 weeks. From weeks 7 to 12, mice were challenged intranasally with house dust mite allergens (HDM) 5 days/week to induce airway inflammation. Lung tissue was analyzed 72 h post-exposure using flow cytometry to assess immune cell populations, and data were analyzed with two-way ANOVA. The ketogenic diet increased body weight in allergen-exposed mice, with a greater effect in males than females (p = 0.0512). Significant sex–diet interactions were noted for alveolar macrophages, CD103⁺, CD11B⁺, and plasmacytoid dendritic cells (p < 0.05). Eosinophil reductions were observed in males but not females on the ketogenic diet. The diet also increased NKT cells and decreased NK cells in males but not females (p < 0.001). These findings highlight sex-specific effects of ketogenic diets on lung immune responses, with stronger impacts in males.

Cadmium (Cd) is a toxic metal widely present in the environment. Certain plant-based natural or active compounds are gaining attention for their neuroprotective effects against chemically induced toxicity. However, there is no report on the impact of bromelain on Cd-induced neurotoxicity, hence the rationale behind this study. Twenty-four adult male rats were divided into four groups: control (normal saline, 5mL/kg), Cd (orally, 5mg/kg), bromelain (50mg/kg), and Cd+bromelain. Rats received bromelain or normal saline for 14 days. Cd was administered concurrently with bromelain and normal saline in the last 7 days. Neurobehavioural responses to locomotion, cognition, anxiety, and depression were assessed. Plasma was assayed for the levels of superoxide dismutase (SOD) and malondialdehyde (MDA), while the prefrontal cortex (PFC) was processed for the concentration of Cd and levels of SOD, MDA, nitric oxide (NO), acetylcholinesterase (AChE), interleukin-6 (IL-6), and tumour necrotic factor-α (TNF-α). Data were analysed using one-way ANOVA (Tukey’s post hoc), with the level of significance set at p<0.05. Exposure to Cd caused a significant behavioural deficit, as indicated by a decline in motor coordination, memory index, and enhanced depressive and anxiety-like behaviours. Biochemically, Cd concentration was significantly increased in the PFC of Cd group compared to the control. There was a reduction in the level of SOD and increased levels of MDA, NO, IL-6, AChE, and TNF-α following Cd exposure. Bromelain significantly improved the behavioural outcomes and reversed some of the biochemical markers altered by Cd toxicity. Bromelain reduced neurobehavioural impairment, cholinergic alteration, and oxido-inflammatory deficits induced by Cd exposure.

Background Taxanes such as paclitaxel (PTX) induce dose-dependent chemotherapy-induced peripheral neuropathy (CIPN), which is associated with debilitating chronic pain and gait impairment. Increased macrophage-related proinflammatory activities have been reported to mediate the development and maintenance of neuropathic pain. While spinal cord stimulation (SCS) has been used for a number of pain conditions, the mechanisms supporting its use for CIPN remain to be elucidated. Thus, we aimed to examine whether SCS can attenuate Schwann cell-mediated and macrophage-mediated neuroinflammation in the sciatic nerve of Rowlette Nude (RNU) rats with PTX-induced gait impairment and mechanical hypersensitivity. Methods Adult male tumor-bearing RNU rats were used for this study examining PTX treatment and SCS. Gait and mechanical hypersensitivity were assessed weekly. Cytokines, gene expression, macrophage infiltration and polarisation, nerve morphology and Schwann cells were examined in sciatic nerves using multiplex immunoassay, bulk RNA sequencing, histochemistry and immunohistochemistry techniques. Results SCS (50 Hz, 0.2 milliseconds, 80% motor threshold) attenuated the development of mechanical hypersensitivity (20.93±0.80 vs 12.23±2.71 grams, pConclusion SCS may attenuate PTX-induced pain and temporal gait impairment, which may be partly attributed to decreases in Schwann cell loss and macrophage-mediated neuroinflammation in sciatic nerves.

Background Emotional derangement contributes to the worsening quality of life in a patient suffering from neuropathic pain (NP). Here, we report the therapeutic beneficial effects of combined acetaminophen and L-carnosine treatment in chronic constriction injury (CCI)-induced NP and associated comorbidities in male Wistar rats. Methods Seven experimental groups of male wistar rats were treated with normal saline, acetaminophen or acetaminophen and L-carnosine. Tail-immersion, Elevated Zero-maze, and light/dark box were used to assess pain and anxiety-like behaviours in rats. The kidney and liver were subjected to histotoxicological assessment after twenty-one days of treatments. Results Thermal hyperalgesia as well as pronounced anxiety-like behaviours were evident in CCI-induced rats. Ligated Wistar showed a significant (p < 0.001) increase in time spent in the close arms and decreased time duration in open arms compared with the unligated control in zero-maze. There was a significant decrease (p > 0.05) in time duration in the lightened compartment and an increase in time duration in the dark compartment of the light and dark box in ligated rats compared with unligated rats. Treatment with acetaminophen or its combination with L-carnosine improved the anxiolytic-like comorbid and pain behaviours in ligated rats. Combined acetaminophen and L-carnosine therapy prevented hepato-and-nephrotoxicity that is characterized in rats treated with acetaminophen alone. Conclusion Hence, combined acetaminophen and L-carnosine treatment is a potential treatment for CCI pain and its comorbidities.

Bamidele Victor Owoyele, Ahmed Olalekan Bakare, Olutayo Folajimi Olaseinde, Mohammed Jelil Ochu, Akorede Munirdeen Yusuff, Favour Ekebafe, Oluwadamilare Lanre Fogabi, and Roi Treister. Korean J Pain 2022;35:488. https://doi.org/10.3344/kjp.2022.35.4.488

Bamidele Victor Owoyele, Ahmed Olalekan Bakare, Olutayo Folajimi Olaseinde, Mohammed Jelil Ochu, Akorede Munirdeen Yusuff, Favour Ekebafe, Oluwadamilare Lanre Fogabi, and Treister Roi. Korean J Pain 2022;35:271-9. https://doi.org/10.3344/kjp.2022.35.3.271

Objectives: This study investigated the antinociceptive effects of co‐administration of lithium chloride (LiCl) and vitamin E (Vit E) on chronic constriction injury (CCI)‐induced peripheral neuropathy in male Wistar rats. It further explored the anti‐inflammatory and neuroprotective properties of LiCl and Vit E, which may be complementary to the antinociceptive effects of the two substances.Methods: Thirty‐six male Wistar rats, 190.00 ± 10.00 g of body weight were randomly assigned to 6 experimental groups and administered with normal saline, Vit E, LiCl, or their combination, once daily for 21 days. CCI was used to induce neuropathic pain (NP) and mechanical allodynia was assessed using von Frey filaments and pinprick test. Open field maze (OFM) was used to assess the exploratory behavior. Biochemical parameters were assessed in the dorsal root ganglion after 21 days of treatment.Results: Mechanical allodynia was developed in rats following CCI. Co‐administration of LiCl and Vit E synergistically reduced mechanical hyperalgesia in rats which were significantly different compared with the single administration of either Vit E or LiCl. Combined doses of Vit E and LiCl significantly increases the explorative behavior in the OFM. CCI increased malondialdehyde (MDA), tumor necrotic factor‐alpha (TNF‐α), calcitonin gene‐related polypeptide, calcium ion (Ca²⁺), and reduced superoxide dismutase (SOD) activities. Co‐administration of LiCl and Vit E significantly reduced MDA, TNF‐α, but increased SOD compared with ligated control.Discussion: The findings revealed that the synergistic effects of the co‐administration of Vit E and LiCl in ameliorating NP are mediated by their anti‐inflammatory and antioxidant properties.

The involvement of pro-inflammatory mediators complicates the complex mechanism in neuropathic pain (NP). This study investigated the roles of bromelain against pro-inflammatory mediators as a mechanism that underpins its antinociceptive and anti-anxiety effects in the peripheral model of NP. Sixty-four male Wistar rats randomly divided into eight groups, were used for the study. A chronic constriction injury model of peripheral neuropathy was used to induce NP. Tail-immersion and von Frey filaments tests were used to assess hyperalgesia while open field and elevated plus mazes were used to assess anxiety-like behaviour. NF-кB, iNOS, nitrate, and pro-inflammatory cytokines were investigated in the plasma, sciatic nerve, and brain tissues using ELISA, spectrophotometer, and immunohistochemistry techniques after twenty-one days of treatment. Bromelain significantly (p < 0.05) improved the cardinal signs of NP and inhibited anxiety-like behaviours in ligated Wistar rats. It mitigated the increases in cerebral cortex interleukin (IL) -1β, IL-6, and PGE₂ levels. Bromelain reduced NF-кB, IL-1β, IL-6, TNF-α, PGE_2, and nitrate concentrations as well as the expression of iNOS in the sciatic nerve. Hence, the antinociceptive and anxiolytic effects of bromelain in the sciatic nerve ligation model of NP is in part due to its ability to reduce nitrosative and inflammatory activities.