Editors' ChoicePain

A one-two punch for pain control

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Science Translational Medicine  27 Apr 2016:
Vol. 8, Issue 336, pp. 336ec69
DOI: 10.1126/scitranslmed.aaf8773

Neuropathic pain is a debilitating pain condition caused by damage to the nervous system. Affecting 5 to 10% of the population, neuropathic pain is commonly associated with spinal cord injury, multiple sclerosis, diabetes, and HIV. Conventional treatment includes antidepressants, calcium channel ligands (e.g., gabapentin), and stronger medications (e.g., opioids) when warranted. Nonetheless, only ~50% of patients manage to escape their neuropathic pain, which can feel like electric shocks and may be associated with numbness or a burning sensation. Innovative treatment strategies are needed that not only are effective in more patients, but also have fewer side effects, including addiction.

In a recent study, Xie and co-workers engineered a multifunctional nanoparticle delivery system that provided sustained neuropathic pain relief in a mouse model of chronic constriction injury. The mesoporous silica nanoparticles, which were ~80 nm in diameter, were loaded with two drugs using two distinct portions of the particle: the surface and the pores. The analgesic Δ9-tetrahydrocannabinol (THC), which functions through cannabinoid receptors in the nervous system, was loaded into the nanoparticle pores. Upon delivery, the THC was released into the bloodstream by diffusion. The second drug, ARA290, an erythropoietin-derived peptide with tissue-protective activity, was conjugated to the silica nanoparticle surface via a disulfide bond. This bond breaks in the vicinity of neural damage where the reducing agent glutathione is present in increased concentrations.

When tested on primary mouse microglia cultures, the drug-loaded silica nanoparticles reduced the inflammatory response to a lipopolysaccharide challenge without affecting microglia viability. The authors then dosed mice that had sustained a chronic restriction injury with the nanoparticles at 7 and 11 days after injury. Whereas single drug–loaded particles modestly reduced sensory and heat-induced pain responses, THC-ARA290–loaded particles relieved pain for a period of 3 weeks. These results were supported by cytokine expression data showing decreased levels of proinflammatory cytokines (e.g., TNF-α) and increased levels of anti-inflammatory cytokines (e.g., IL-10). Future work is needed to confirm the efficacy and safety of these nanoparticles in other animal models of neuropathic pain.

J. Xie et al., Mesoporous silica particles as a multifunctional delivery system for pain relief in experimental neuropathy. Adv. Healthc. Mater. 10.1002/adhm.201500996 (2016). [Abstract]

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