In the study of Van Daele et al. (2002), injection of onabotulinumtoxinA into the tight and painful sternocleidomastoid muscle relieved the pain and tightness in four of six patients. All patients had received radiotherapy for head and neck cancer. The injected dose was 20–25 units administered at 1 or 2 points into the sternocleidomastoid muscle.

Anecdotal case reports have also described marked reduction of postradiation pain after local BoNT-A injection. As an example, a 75-year-old gentleman with rectal cancer developed severe rectal pain and a large noncancerous rectal ulcer after local resection and radiation. Injection of onaA into the rectal wall at multiple sites reduced the pain dramatically and helped healing of the ulcer (De Micheli et al. 2003).

Stubblefield et al. (2008) also found BoNT-A injection helpful in relieving focal pain caused by radiation fibrosis. In this retrospective study of 23 patients, 30 % had painful trismus, and 43 % had trigeminal and cervical plexus neuralgia.

Voung et al. (2011) studied the effect of BoNT injection into the rectal wall immediately after high-dose-rate endorectal brachytherapy (HDREBT) in 15 patients with prostatic cancer. The patients who received 100 units of onaA into the rectal wall had a lower incidence of acute radiation prostatitis with significant reduction of bowel frequency and urgency (P < 0.05) and lesser degrees of pain (P = 0.07).

In another study (Bach et al. 2012) of nine patients with postsurgical contracture of sternocleidomastoid or pectoralis major muscle related to head and neck cancer, patients expressed pain relief after administration of aboA into sternocleidomastoid muscle (100–400 units) or the pectoralis muscle flap (125–200 units) with no side effects. Injections were administered at four to five locations into sternocleidomastoid muscle or into the pectoralis muscle flap.

Wittekindt et al. (2006) examined the efficacy of BoNT-A (type not specified) in 23 patients who reported neuropathic pain in the neck and shoulder following neck dissection for squamous cell carcinoma of upper “aerodigestive tract.” BoNT-A was diluted by 1 or 2 cc preservative-free saline before administration. Patients were divided into low-dose (80–120 units) and high-dose (160–240 units) groups. Patients and physicians were blinded to the dose of injections. Injections were performed in 8–12 locations subcutaneously into targeted neck and shoulder regions. Patients’ response to BoNT injection was measured by visual analog scale (VAS) at baseline prior to injections and at day 28 after injections. The mean baseline pain was 4.3 on VAS (0–10). The quality of life was evaluated by a questionnaire from the European Organization for Research and Treatment of Cancer (EORTC), specifically prepared for head and neck cancers, at the same time frames. At day 28, mean VAS score for the low-dose group changed from 4.3 to 3.6 (P < 0.05), but the change for the high-dose group was not significant. Furthermore, the low-dose group also showed a trend for improvement of quality of life.

In another prospective study (Hartl et al. 2008), the efficacy of onabotulinumtoxinA (onaA) and abobotulinumtoxinA (aboA) was assessed in 19 patients with nasopharyngeal and oropharyngeal cancer who developed severe spasm of masseter muscles and trismus, on the average, 5.6 years after radiotherapy for cancer. Eleven patients had received chemotherapy in addition to radiation. The location of cancers was in the nasopharynx (n = 3), oropharynx (n = 9), oral cavity (n = 2), oral cavity and nasopharynx (n = 1), larynx (n = 3), and parotid gland (n = 1). Each masseter muscle was injected at two points, either with onaA (50 units) or aboA (250 units). At 4 weeks postinjection, pain, spasms, and functional score (measured in a 20 subset questionnaire) all improved significantly compared to baseline (P = 0.002, P = 0.004, P = 0.04, respectively). No difference was noted between onaA and aboA.

We are currently studying the effect of incobotulinumtoxinA (incoA) on moderate to severe focal pain (VAS >5) at the site of cancer resection or cancer radiation. Patients had had radiation and surgery for breast or head and neck cancer. Efficacy of treatment is measured by VAS, patient global impression of change (PGIC), and Quality of Life Scale for pain at 4, 6, 8, 10, and 12 weeks postinjection. The primary outcome is two grades or more improvement in VAS with additional patient satisfaction expressed in PGIC at 4 weeks. The secondary outcome is improvement of quality of life at 6 weeks. A total of up to 100 units of incobotulinumtoxinA, diluted in 1 cc of saline, was injected into the area of local pain indicated by the patient. The injections were both subcutaneous and intramuscular. The target number of the study is 20 patients. The preliminary results (Rostami et al. 2014) of this open-label prospective study are presented below. To date, 12 patients were enrolled in the study, and 10 patients completed the assessments. Two patients died during the study from complications of cancer and were removed from the final analysis. Of the remaining ten who completed the study, eight patients demonstrated significant reduction of pain and improvement of both quality of life and patient impression of change 6 weeks postinjection. The mean VAS of 7.4 at baseline was lowered to 3.8 at week 6 (P < 0.05). These positive results agree with our previous retrospective report of seven cancer patients with local postradiation/postsurgical pain (Mittal et al. 2012). In these seven patients, intramuscular injection of 80–160 units of onabotulinumtoxinA (onaA) reduced the local pain at 4 weeks postinjection. Both types of BoNT-A (inco and ona) seemed to be equally effective against pain. None of the patients developed any side effects in either of the prospective or the retrospective study.