Use of Botulinum toxin in chronic pain conditions:
Myofascial pain syndrome:
Myofascial pain is regional in location and commonly involves muscular trigger points (MTPs). Trigger points are characterized by focal areas of muscular tissue that are not only tender to palpation, but also may trigger pain distant from the actual site, known as ‘referred’ pain. A twitch response of the palpated trigger point is commonly seen. The mechanism of pain is believed to be due to a dysfunctional motor end plate causing an excess of Ach release leading to excessive muscular contraction and spasm. MTPs are commonly treated with local injections of anesthetic but also have benefited from dry needling alone. BoNT-A appears to be a reasonable injectate. BoNT-A has been shown to provide relief in pain and improvement in function for patients with chronic low back pain due to muscular dysfunction. There is no consensus as to the dosing of BoNT-A for myofascial pain disorders.
Plantar fasciitis is a common pain syndrome involving the plantar fascia, characterized by exquisite tenderness over the medial aspect of the calcaneal tuberosity, exacerbated upon weight bearing. The pain mechanism of plantar fasciitis is believed to involve hypertrophy and micro tears of the plantar fascia with secondary inflammation and spasm of the underlying foot musculature. Plantar fasciitis is commonly treated with physiotherapy, orthotics and at times steroid injections. Babcock et al showed a significant benefit in analgesia with BoNT-A injections compared to placebo.
Piriformis syndrome can cause buttock pain with radiation in a sciatic distribution. Patients usually present with exquisite pain upon piriformis palpation that is exacerbated with hip flexion combined with hip internal rotation. There are variable anatomic findings of the sciatic nerve in relation to the piriformis. Spasm and tightening of the piriformis muscle can irritate the sciatic nerve, thus imitating lumbar discogenic referred pain. There are limited studies for BoNT-A injections for piriformis syndrome; however, Childers and colleagues showed analgesic benefit from BoNT-A injections into the piriformis under electromyography and fluoroscopy guidance.
Botulinum toxin type A has been recommended by NICE as an option for the prophylaxis of headaches in adults with chronic migraine (defined as headaches on at least 15 days per month of which at least 8 days are with migraine)that has not responded to at least three prior pharmacological prophylaxis therapies and whose condition is appropriately managed for medication overuse. A positive response is defined as at least a 30% reduction in headache days per month after two treatment cycles. The antinociception mechanism is based not on the acetylcholinergic mechanism but rather on the inhibition of neuropeptides including substance P, CRGP, and glutamate at afferent nerve endings. In turn, neurogenic inflammation is inhibited, thus decreasing peripheral sensitization and indirectly overall central sensitization.
Osteoarthritis (OA) is the most common form of arthritis that affects primarily large weight-bearing joints such as the knees and hips, but also affects the spine, hands, and shoulders. OA is commonly treated with physiotherapy, oral anti-inflammatory medications, and intra-articular steroid joint injections. Mahowald and colleagues performed intra-articular BoNT-A injections on patients with OA and RA who were refractory to oral anti-inflammatory and analgesic agents. All the patients had a history of either intra-articular steroid or viscosupplement injections with no significant benefit. BoNT-A intra-articular injections into the knees, ankles, and shoulders showed a significant reduction in pain as well as improved active range of motion.
Botulinum toxin has also been applied to a variety of neuropathic pain conditions. Diabetic neuropathy is one of the most common neuropathies seen today. The pathophysiology of neuropathic pain is complex and is hypothesized to involve local tissue damage in the periphery resulting in damage to the afferent C fibers and A-delta fibers. Consequently, nociceptor thresholds are diminished and neuroplasticity occurs including increased sodium channels and an upregulation of the N-methyl-D-aspartate receptors involved in neuropathic pain transmission. In a double-blind crossover trial, Yuan and colleagues showed a reduction in pain upon injection of BoNT-A vs placebo into the dorsum of the feet of patients with diabetic neuropathy.
Botulinum toxin is contraindicated in patients with known hypersensitivity to botulinum toxin type A or to any of the excipients. It should only be used with extreme caution and under close supervision in patients with subclinical or clinical evidence of defective neuromuscular transmission (e.g. myasthenia gravis or Lambert-Eaton Syndrome), in patients with peripheral motor neuropathic diseases (e.g. amyotrophic lateral sclerosis or motor neuropathy) and in patients with underlying neurological disorders. Such patients may have an increased sensitivity Botulinum toxin, even at therapeutic doses, which may result in excessive muscle weakness and an increased risk of clinically significant systemic effects including severe dysphagia and respiratory compromise. The botulinum toxin product should be used under specialist supervision in these patients and should only be used if the benefit of treatment is considered to outweigh the risk. Patients with a history of dysphagia and aspiration should be treated with extreme caution.