Preemptive minocycline decreases allodynia and depressive-like behaviors in a peripheral neuropathy rat model: a preliminary study

Background and Objective The neuroimmune system plays a critical role at all phases of chronic pain including at its onset. We therefore hypothesized that preemptive immunomodulation could decrease susceptibility and/or offer protection to pain.

Six days before the spared nerve injury (SNI), Wistar Han rats were treated with either the immunomodulator minocycline (MIN) or vehicle (VEH). After that, half of the animals from each group switch treatments for additional 7 days, resulting in 4 groups: continuous treatment (MIN/MIN), pretreatment (MIN/VEH), early treatment (VEH/MIN) and the control (VEH/VEH). Mechanical allodynia was recorded using Von Frey test until 4 weeks after SNI where depressive-like behaviors of the animals were also assessed using sucrose preference test.

The continuous treatment provided sustained protection against mechanical allodynia, with rats in this group showing a significantly higher threshold to pain sensitivity compared to those in VEH/VEH. In contrast, pain relief effects were not observed with MIN/VEH and VEH/MIN. Additionally, animals in MIN/MIN, and VEH/MIN exhibited decreased anhedonic-like behavior at 30 days after SNI, relative to the control.

The exposure to an anti-inflammatory drug circa the installation of a neuropathic lesion had a positive impact on allodynia and on anhedonic behavior for a relatively long period after treatment cessation. The results support the assertions that pain trajectories can be altered at pain early stages by targeting the neuroimmune system. This proof-of-concept has the potential to be broadened to other drugs and/or therapeutical schemes. Highlights Chronic pain susceptibility varies across individuals. (endo)phenotypes of susceptibility manifest prior/circa pain onset. Preemptive minocycline treatment transiently decreases allodynia. Preemptive minocycline treatment provides sustained reduction of depressive-like behavior. Immune system modulation prior to pain onset or at early stages have beneficial outcomes. Competing Interest Statement The authors have declared no competing interest.