Future Directions in Pain Management

Abstract

Treatment for chronic, locoregional pain ranks among the most prevalent unmet medical needs. The failure of systemic analgesic drugs, such as opioids, is often due to their off-target toxicity, development of tolerance, and abuse potential. Interventional pain procedures provide target specificity but lack pharmacologically selective agents with long-term efficacy. Gene therapy vectors are a new tool for the development of molecularly selective pain therapies, which have already been proved to provide durable analgesia in preclinical models. Taken together, advances in image-guided delivery and gene therapy may lead to a new class of dual selective analgesic treatments integrating the molecular selectivity of analgesic genes with the anatomic selectivity of interventional delivery techniques.

Mechanisms of Pain in Sickle Cell Disease

“…Thus, in addition to pharmacologics, integrative approaches ofer the potential to reduce sickle pain. Finally, gene therapy vectors are a new tool for the development of molecularly selective pain therapies, which have been shown to provide reliable analgesia in preclinical models [123]. The use of gene therapy may lead to a new class of analgesic treatments based on the molecular selectivity of analgesic genes.…”

Peripherally targeted analgesia via AAV-mediated sensory neuron–specific inhibition of multiple pronociceptive sodium channels

“…In preclinical models, direct DRG delivery of AAVs encoding analgesic biologics can provide relief in chronic pain, with high transduction efficiency, flexibility for selective segmental localization, and minimal behavior changes attributable to the surgical procedure ( 71 ). In parallel, injection techniques are being advanced to achieve minimal invasive delivery of biologics for future clinical pain therapy ( 72 , 73 ). Small peptides derived from the target protein sequences can serve as decoy molecules to selectively interfere with the function of their target signaling proteins by preemptively binding to them ( 13 ).…”

Targeting intrinsically disordered regions facilitates discovery of calcium channels 3.2 inhibitory peptides for adeno-associated virus–mediated peripheral analgesia

“…9,51,93 In parallel, injection techniques are being advanced to achieve minimally invasive delivery of biologics for future clinical pain therapy. [66][67][68] Small peptides that mimic target protein sequences can serve as decoy molecules to selectively interfere with the function of their target signaling protein by preemptively binding to it. 25,93 We have successfully used this strategy in rat models to induce analgesia by preventing assembly of functional transient receptor potential cation channel subfamily V member 1 (TrpV1) channels 87 and by blocking membrane trafficking of Ca V 2.2 channels by interrupting their interactions with the structural protein collapsin response mediator protein 2 (CRMP2).…”