SmallRNA seq of leukocytes of chronic pain patients (CRPS, Nerve lesion and Diabetes polyneuropathy) and an SNI mice model ncRNA pain consortium

Chronic neuropathic pain is widespread, but individual diagnostic biomarkers are unknown and primate specificity hampers rodent validation tests. Here, we report that microRNA (miR)-sequencing of blood leukocytes from 250 multi-centre pain patients revealed complex regional pain syndrome (CRPS)-related increases in the pain-related microRNA (miR)-21-5p and decreases in the cholinergic-targeted miR-335-5p. Both these miRs were similarly modified in dorsal root ganglia of nerve-injured mice, where long RNA-sequencing detected pain-associated elevation of neurogenesis and inflammation-related transcripts. Moreover, either genomic ablation or intrathecal antisense oligonucleotide neuro-suppression of miR-21a-5p, but not genetic debilitation of B7-H1 lymphocytes alleviated murine pain responses while reducing cellular pathways that are induced in patients’ leukocytes; and a cooperative leukocyte ‘signature’ of 12 miRs including miR-21a-5p and -335-5p predicted 96% of CRPS symptoms severity. Our findings implicate cholinergic-suppressible neuro-inflammation processes in chronic acute pain, suggest pathway-based cooperative validation tests and open unprecedented options for mechanistic studies of chronic pain disorders. 250 leukocyte samples of chronic pain patients and matching healthy healing/ painless and heathy controls, in addition 3 mice per treatment group of sciatic nerve injured (SNI), SHAM and naïve.