Isolation, characterization and testing of RNA aptamers targeting glutamate receptors in a rat spinal cord injury pain model

Spinal cord injury (SCI)-induced neuropathic pain remains difficult to treat. Given the high risk of using opioid analgesics as a primary treatment option, developing non-opioid therapeutic candidates is desirable. Studies in preclinical pain models have shown that antagonists of the ionotropic glutamate receptors (iGluRs) can inhibit pain without abuse potential. Here we report the first study of making and testing a group of RNA aptamers that inhibit iGluRs in a rat SCI pain model. Our results show that aptamers are efficacious in alleviating evoked and ongoing neuropathic symptoms in rats without any significant adverse effects. Furthermore, the antinociceptive efficacy of RNA aptamers on both tactile and cold hypersensitivity becomes steadily strengthened during repeated aptamer administrations and the antinociceptive protection persists for 2-3 extra weeks after the termination of intrathecal injection of aptamers. We also note potential sex differences in aptamer treatment, suggesting the possibility of tailoring the use of aptamers in sex-specific pain treatment. This study demonstrates that developing aptamers targeting iGluRs, especially kainate receptors, as potential analgesic candidates for treatment of SCI-induced pain, is promising.