Selective neuronal silencing using synthetic botulinum molecules alleviates chronic pain in mice
Chronic pain affects more than 25 million Americans and is associated with reduced life span, anxiety, and depression. Opioid administration is often effective in relieving pain but, unfortunately, opioids have serious side effects, including risk of addiction and overdose.
In a new study, Maiaru et al. have leveraged the inhibitory effects of botulinum toxin on neuronal activity. They developed two botulinum-conjugated molecules (SP-BOT and Derm-BOT) that were able to silence subpopulations of pain-related spinal neurons in several mouse models of chronic pain. Intrathecal administration of one dose of SP-BOT or Derm-BOT produced long-term pain relief in the mouse models that was comparable to the effects of opioid treatment. The results suggest that botulinum-conjugated molecules could be an opioid-free alternative for treating chronic pain.
Chronic pain is a widespread debilitating condition affecting millions of people worldwide. Although several pharmacological treatments for relieving chronic pain have been developed, they require frequent chronic administration and are often associated with severe adverse events, including overdose and addiction.
Persistent increased sensitization of neuronal subpopulations of the peripheral and central nervous system has been recognized as a central mechanism mediating chronic pain, suggesting that inhibition of specific neuronal subpopulations might produce antinociceptive effects. We leveraged the neurotoxic properties of the botulinum toxin to specifically silence key pain-processing neurons in the spinal cords of mice. We show that a single intrathecal injection of botulinum toxin conjugates produced long-lasting pain relief in mouse models of inflammatory and neuropathic pain without toxic side effects.
Our results suggest that this strategy might be a safe and effective approach for relieving chronic pain while avoiding the adverse events associated with repeated chronic drug administration.
18 Jul 2018http://stm.sciencemag.org/