Botulinum Neurotoxin for Pain Management: Insights from Animal Models

Abstract

The action of botulinum neurotoxins (BoNTs) at the neuromuscular junction has been extensively investigated and knowledge gained in this field laid the foundation for the use of BoNTs in human pathologies characterized by excessive muscle contractions. Although much more is known about the action of BoNTs on the peripheral system, growing evidence has demonstrated several effects also at the central level. Pain conditions, with special regard to neuropathic and intractable pain, are some of the pathological states that have been recently treated with BoNTs with beneficial effects. The knowledge of the action and potentiality of BoNTs utilization against pain, with emphasis for its possible use in modulation and alleviation of chronic pain, still represents an outstanding challenge for experimental research. This review highlights recent findings on the effects of BoNTs in animal pain models.

Botulinum toxin A, brain and pain

“…Later, its efficacy in reducing mechanical allodynia was reported in sciatic nerve constriction-injury-evoked neuropathy (Luvisetto et al, 2007;Marinelli et al, 2010;Mika et al, 2011). It was observed that BoNT/A accelerates the functional recovery of the injured sciatic nerve in a model of sciatic constriction injury-induced peripheral neuropathy, measured using sciatic static index and regeneration-associated markers (Marinelli et al, 2010;Mika et al, 2011;Pavone and Luvisetto 2010). In addition, BoNT/A prevented the sciatic nerve injury-induced upregulation of pronociceptive opioid neuropeptides and SNAP-25 in the sensory ganglia, and markers of glial activation in the spinal cord (Mika et al, 2011;Vacca et al, 2013).…”

Involvement of μ-opioid receptors in antinociceptive action of botulinum toxin type A

“…Apart from its effect on neuromuscular junction, recent preclinical and clinical studies reported the efficacy of BTX-A in reduction of allodynia and hyperalgesia in pain of different origins (Jabbari and Machado 2011;Pavone and Luvisetto, 2010). Moreover, BTX-A was recently registered for treatment of chronic migraine (Dodick et al, 2010) and several controlled clinical studies in other painful conditions are in progress (Jabbari and Machado, 2011;Singh, 2010).…”

Antinociceptive effect of botulinum toxin type A on experimental abdominal pain

“…In contrast to different types of somatic pain (reviewed by Pavone andLuvisetto, 2010, Matak and) the information related to the beneficial action of BTX-A on pain arising from the viscera is mostly limited to the pelvic region. It was found that local BTX-A injections efficiently decrease pain in patients suffering from bladder pain syndrome/ interstitial cystitis, prostatitis and pelvic-floor muscle disorder (Abbott et al, 2006., Chung et al, 2012, El-Khawand et al, 2013, Gottsch et al, 2011, Kuo, 2013, Pinto et al, 2013, Smith et al, 2004, Zermann et al, 2000.…”

“…application, BTX-A failed to affect pain induced by acetic acid, thus indicating that BTX-A's antinociceptive action is predominantly of spinal origin. Since studies on different models of somatic pain demonstrated the antinociceptive effect of BTX-A after peripheral, subcutaneous application (reviewed by Pavone andLuvisetto, 2010, Matak and), here we investigated the effect of i.p. applied BTX-A.…”

“…This enables its therapeutic use in disorders characterized by overactive muscles, overactive exocrine glands and, most recently, non-muscular pain conditions (reviewed by Dressler, 2013, Matak and. Antinociceptive activity of BTX-A was demonstrated in various preclinical (reviewed by Pavone and Luvisetto, 2010) and clinical studies (reviewed by Jabbari and Machado, 2011) during the last decade. It was shown that a single injection reduces pain over a prolonged period of time (several months), which represents the unique feature of BTX-A among available analgesics.…”