Table 1 Baseline characteristics Characteristic Mean age, years (range) Female sex (%) Ongoing claims Mean duration of pain, months (SD) Neck pain severity, mean VAS (SD) Mean number of neck pain days, % (SD) Mean neck pain duration per day, hours (SD) Mean number of medication days, % (SD) Mean number of analgesics per day, tablets (SD) Mean total cervical range of motion, degrees (SD) *1 = one missing data; *3 = three missing data Table 2 Improvement scale At 4 weeks Great worsening 4 Any worsening 2 No improvement 6 Any improvement 5 Great improvement 2 Total 19*1 *1 = one missing data Table 3 Secondary outcome measures Outcome Botulinum toxin (n = 20) 39 (20–58) 14 (70%) 15 (75%) 40 (71) 64.5 (14.8) 97% (11) *1 12.7 (4.0) *3 50% (41) *1 1.4 (1.9) 266 (73) *1 2 4 7 4 3 20 96% (12) 89% (25) *2 7% (22) 11.7 (4.5) 11.0 (5.1) *2 0.72 (4.7) 35% (40%) 24% (32%) *2 5.7% (24%) 1.3 (2.1) 0.95 (1.9) *1 0.18 (0.6) 266 (60) *1 277 (62) *3 11 (36) 293 Placebo (n = 20) 34 (20–49) 13 (65%) 18 (90%) 37 (20) 62.1 (20.3) 96% (12) 11.7 (4.5) 36% (40) 1.3 (2.1) 266 (60) *1 2 3 8 4 3 20 )1% ()15% to + 13%) )0.14 ()3.0 to + 2.7) 0.7% ()15% to + 13%) )0.14 ()0.6 to + 0.4) )11 ()40 to + 17) 0 4 8 5 3 20 At 8 weeks 0 1 8 5 6 20 At 12 weeks 1 2 6 5 6 20 Botulinum toxin (n = 20) Placebo (n = 20) Therapeutic gain (95% CI) Improvement Botulinum toxin (n = 20) Placebo (n = 20) Botulinum toxin (n = 20) Placebo (n = 20) Botulinum toxin (n = 20) Placebo (n = 20) Neck pain days (% ± SD) Baseline (4 weeks) 97% (11) *1 Post-treatment (12 weeks) 89% (23) *2 Mean difference 8% (18) Neck pain duration (hours/day ± SD) Baseline (4 weeks) 12.7 (4.0) *3 Post-treatment (12 weeks) 12.2 (4.6) *7 Mean difference 0.86 (2.2) Days on which analgesics were taken (% ± SD) Baseline (4 weeks) 49% (42%) Post-treatment (12 weeks) 42% (38%) *3 Mean difference 6.4% (16%) Number of analgesics taken per day (tablets/day ± SD) Baseline (4 weeks) 1.4 (1.9) *1 Post-treatment (12 weeks) 1.2 (1.8) *2 Mean difference 0.32 (0.8) Total cervical range of motion (degrees ± SD) Baseline 266 (73) *1 Post-treatment (week 12) 293 (59) *2 Mean difference 22 (43) *1 = one missing data; *2 = two missing data; *3 = three missing data *7 = seven missing data Patients with chronic whiplash syndrome also form a very heterogeneous group, with a wide spec- trum of symptoms, varying from neck pain to head- ache, with pain of different degrees. Many different factors seem to play a role in the development of acute and chronic pain after a whiplash injury. There is ample evidence that central mechanisms might play a more important role in the development of chronic neck pain in whiplash patients [4], as in other chronic pain syndromes. Damaged peripheral tissue releases inﬂammatory mediators (like bradykinine and prostaglandins) that changes