Neuropathic pain results from injuries or diseases affecting the somatosensory system, impacting 7-10% of the global population. Animal models with chronic constriction injury (CCI) of the sciatic nerve are essential for investigating its pathophysiology. Although pharmacological treatment is widely used for neuropathic pain, non-pharmacological interventions such as environmental enrichment (EE) and voluntary exercise (VE) have shown promising efficacy. EE, which provides motor, sensory, social, and cognitive stimuli, can be enhanced by VE, performed in a freely accessible activity wheel. However, there is a scarcity of studies comparing isolated EE and its combination with VE.

To evaluate the effects of EE, alone or combined with VE, on sensitivity modulation in a model of neuropathic pain induced by sciatic nerve constriction in female mice.

Twenty female BALB-C mice, aged 7-8 weeks and weighing 30-35 g, were used, acquired after approval by the animal research ethics committee. The 29-day experiment divided the animals into four groups: CCI; CCI + VE; SHAM, and SHAM + VE. All groups underwent EE, and the SHAM group consisted of animals without sciatic nerve injury. Sensitivity was assessed using the Von Frey test, which applies stimuli with nylon monofilaments (0.05 to 300 g) to the animal&apos;s paw, with an expected response of shaking, cleaning, or lifting the paw if the stimulus is felt. Each filament was applied 10 times, and a positive result occurred when the animal responded 40% of the time to the same filament. Tests were conducted before injury and on days 7, 14, 21, and 28 post-CCI. Statistical analyses included the Shapiro-Wilk normality test and one-way ANOVA with Tukey&apos;s post hoc test, using Prism 9 software. p-values < 0.05 were considered significant.

In the Von Frey sensory test, all groups showed worsened sensitivity on day 7, with no significant differences (p = 0.89). On day 14, the CCI + VE group improved, matching the SHAM group, while the CCI group maintained significantly worse sensitivity compared to the other groups (one-way ANOVA, F (3,11) = 5.6; p = 0.001). On days 21 and 28, the CCI group aligned with the SHAM and CCI + VE groups (p = 0.35).

VE combined with EE accelerated the recovery of the CCI + VE group, which showed a faster improvement in mechanical sensitivity starting on day 14, compared to the CCI group, which only improved from day 21 onwards.

The findings suggest that the combined intervention may be a more effective strategy for neuropathic pain modulation. Translating to clinical practice, outdoor or group exercises are recommended as a form of enrichment.