Modulation of Aryl Hydrocarbon Receptor Expression Alleviated Neuropathic Pain in a Chronic Constriction Nerve Injury Animal Model

Neuropathic pain is well known to occur after damage to the somatosensory system. Aryl hydrocarbon receptor (AhR) has neuroprotective effects when the central nervous system is subjected to internal and external stimulations. However, the exact mechanism by which AhR regulates neuropathic pain is poorly understood. Nerve explant culture and the chronic constrictive nerve injury (CCI) model in wild or AhR-knockout mice were used in this study. In the nerve explant culture, the ovoid number increased in the AhR-/- condition and was decreased by omeprazole (AhR agonist) in a dose-dependent manner. Increased nerve degeneration and the associated inflammation response appeared in the AhR-/- condition, and these changes were attenuated by omeprazole. High expression of AhR in the injured nerve was noted after CCI. Deletion of AhR aggravated nerve damages and this was restored by omeprazole. Deletion of AhR increased NGF expression and reduced axon number in the paw skin, but this was attenuated by omeprazole. A highly expressed inflammation reaction over the dorsal spinal cord, somatosensory cortex, and hippocampus was noted in the AhR-deleted animals. Administration of omeprazole attenuated not only the inflammatory response, but also the amplitude of somatosensory evoked potential. Deletion of AhR further aggravated the neurobehavior compared with the wild type, but such behavior was attenuated by omeprazole. Chronic constrictive nerve injury augmented AhR expression of the injured nerve, and AhR deletion worsened the damage, while AhR agonist omeprazole counteracted such changes. AhR agonists could be potential candidates for neuropathic pain treatment.

Automated summary

Neuropathic pain is reduced by AhR activation and aggravated by AhR deletion, indicating the neuroprotective effects of AhR. AhR expression is increased after nerve injury, and AhR agonist omeprazole attenuates nerve damage and inflammation. AhR agonists may have potential in neuropathic pain treatment.