Table 1.

Summary of studies of botulinum toxin in osteoarticular pain-efficacy outcomes.

Study: author; number of patients	RCT versus open-label	Intervention and comparison	Mean age in years (SD)/male/female	Mean pain duration in months (SD)	Primary outcome	Main result—efficacy
Tennis elbow
Wong et al. 2005 60 patients	RCT, double-blind, 3 months	Single injection of 60 units of BoNT/A (Dysport) versus saline placebo in SQ tissue and muscle	BoNT: 46 (9) PL: 44 (6)/49 M/11 F	BoNT: 12 (9) PL: 19 (21)	Pain on VAS 0—100mm at 4 and 12 weeks	BoNT: 25.3mm at 4 weeks; 23.5mm at 12 weeks PL: 50.5mm at 4 weeks; 43.5mm at 12 weeks Differences significant at both 4 (p < 0.0001) and 12 weeks (p = 0.0006)
Keizer et al. 2002 40 patients	Randomized, not blinded, 24 months	Surgical release versus one or two injections of 30—40 units BoNT	All pts: 43 years (range, 25—72 years) 19 M/21 F	All pts: 11 (range, 6—48 months)	Pain on VAS, range of motion, sick leave, modified scoring system of pain, function, tenderness, and satisfaction	No difference in pain between groups Range of motion significantly better in BoNT compared to surgery group at 3 and 6 months; no difference at 12 or 24 months Sick leave lower in surgery group versus BoNT group at 3 months (p = 0.01), but no difference at 6, 12 and 24 months Overall score was similar in the two groups at 3, 6, 12 and 24 months
Hayton et al. 2005 40 patients	RCT, double-blind, 3 months	Single injection of 50 units of BoNT/A versus saline placebo intramuscular 5 cm distal to area of maximum tenderness	All pts: 47 years (range, 35—71 years) 21 M/19 F	All pts: 11 range, 6—48 months)	Pain on VAS, grip strength, Short Form 12	Differences in pain scores were not significant at 3 months No significant differences in grip strength or SF-12 scores between groups at 3 months
Facial pain and temporomandibular disorder
Von Lindern, 2001 90 patients	RCT, double-blind, 1—3 months	BoNT/A 35 MU (MU — mouse units) versus placebo injected on each side of masticatory muscle	No information provided	Failed conservative treatment for 3—34 months	Pain on VAS	Reduction in VAS pain at 1—3 months postinjection significantly more in BoNT versus placebo (p < 0.01) Greater proportion with ≥2-point reduction in VAS pain in BoNT/A versus placebo: ∽76% versus 10% (no statistical comparisons)
Low back pain
Foster, 2001 [Foster et al. 2001] 31 patients	RCT, double-blind, 2 months	200 units BoNT/A versus placebo injected into five lumbar or lumbosacral sites on more painful side	BoNT: 47 years (range, 20—73) PL: 46 years (range, 21—65)/15 M/16 F	BoNT: 72 (range, 6—120) PL: 96 (range, 12—360)	Pain on VAS; Oswestry Back Pain Inventory	73% (11/15) patients in BoNT/A group had ≥50% reduction in VAS pain compared to 25% (4/16) in placebo group at 3 weeks (p = 0.012) 60% in BoNT versus 13% in placebo had ≥50% reduction in VAS pain at 8-weeks (p = 0.009) Improvement in Oswestry scores were seen in 67% of BoNT and 19% of placebo-treated patients at 8 weeks (p = 0.011)
Shoulder joint pain
Singh et al. 2009b 36 patients; 43 shoulders	RCT, double-blind, 1 month	100 units of BoNT/A versus placebo into glenohumeral joint	BoNT: 72 (SE, 2) PL: 70 (SE, 3)/35 M/1 F	BoNT: 8 (SE, 2) PL: 11 (SE, 3)	Pain on VAS; drop-out due to treatment failure; shoulder pain and disability index (SPADI) Short Form 36 Short form McGill Pain	Significantly greater reduction in VAS pain in BoNT/A (2.4) versus placebo (0.8) group (p = 0.02) Higher proportion dropped out at 1 month from placebo (45%) than BoNT/A (19%) (p = 0.13) SF-36 scores improved significantly more in BoNT/A versus placebo in 5/8 subscales (p ranging 0.04—0.001) McGill affective dimension scores were significantly greater in BoNT/A versus placebo group (p = 0.047) Trend towards significance in SPADI disability scores (p = 0.083) No significant differences in active flexion, active abduction, SPADI pain and total and McGill sensory and total scores
Hand pain and carpal tunnel syndrome
Breuer et al. 2006 20 patients	RCT, double-blind, 3 months	2500 units BoNT/B M versus placebo injected into three hypothenar muscles in carpal tunnel	No information provided	No information provided	Pain on Numeric Rating Scale (NRS) West Haven-Yale Multidimensional Pain Inventory (WHYMPI)	Pain scores, pain-related sleep disturbances, WHYMPI scores improved in both groups at follow-up, but didn't significantly differ between groups At 6 weeks, 8/10 (80%) BoNT patients versus 6/9 (67%) had clinically meaningful reduction of pain VAS (30% or 2 point reduction). Similar reductions at 13 weeks were 2/7 (29%) BoNT versus 4/9 (44%) of placebo.
Plantar fasciitis
Babcock et al. 2005 27 patients; 43 feet	RCT, double-blind, 2 months	70 units BoNT/A (40 units on medial aspect of the heel and 30 units in the foot arch) versus placebo	All: median age, 44 (range, 21—65) 9M/18F	No information provided	Pain VAS, 0—10cm Pressure algometry response Maryland Foot Score (0—100 points) Pain relief VAS, 0—10cm	At 3 weeks, improvements were significantly higher for BoNT versus placebo: Pain VAS, 2.7 (39% decrease) versus 4.7 (p<0.004); Maryland Foot score, 72 (34%) versus 49 (p = 0.001); pressure algometry, 2.7 (40% increase) versus 1.8 (p = 0.003); and pain improvement scale, 4.8 versus 0.6 (p<0.005) At 8 weeks, improvements were significantly higher for BoNT versus placebo: Pain VAS, 1.6 (56% decrease) versus 4.4 (p<0.005); Maryland Foot score, 81 (47%) versus 54 (p = 0.001); pressure algometry, 2.8 (56% increase) versus 1.8 (p = 0.003); and pain improvement scale, 5.0 versus 1.2 (p < 0.005)

BoNT, botulinum toxin; BoNT/A, Botulinum toxin type A; BoNT/B, Botulinum toxin type B; NRS, Numeric Rating Scale; PL, placebo; pts, patients; RCT, randomized controlled trial; SE, standard error; SF-12, Short Form 12; SPADI, shoulder pain and disability index; SQ, subcutaneous; VAS, Visual Analog Scale; WHYMPI, West Haven-Yale Multidimensional Pain Inventory.