292 partly incomplete (missing data on neck pain dura- tion, days on which medication was taken and mean number of tablets per day). There were no differences in baseline characteristics between the two treatment groups. Neck pain intensity, VAS at baseline was 64.5 mm (SD = 14.8) in the botulinum group and 62.1 (SD = 20.3) in the placebo group (Table 1). At 12 weeks the VAS scores were 52.0 mm (SD = 29.2) in the botulinum group and 56.7 mm (SD = 29.6) in the placebo group. Mean differences between VAS pre- and post-treatment was 12.5 in the botulinum group and 5.5 in the placebo group. The therapeutic gain ( = difference in improvement be- tween the two treatment groups measured in mm) was –7.0 (p = 0.31; 95% CI (–20.7 to + 6.7)). Six patients in the botulinum group were responders as deﬁned, versus four in the placebo group (NS, p = 0.5). Patients’ assessment of improvement/worsening showed no signiﬁcant difference between the two groups at week 4 (p = 0.9), week 8 (p = 0.4) and 12 (p = 0.4) (Table 2). There were no signiﬁcant differences between the two treatment groups in mean number of neck pain days, mean number of neck pain hours per day, mean number of days on which medication was taken, and mean number of tablets taken per day pre- and post- treatment (Table 3). At baseline all patients showed a reduced cervical range of motion (CROM) in all directions [9]. There was a slight improvement in total CROM in favour of the botulinum group. However, CROM was not sig- niﬁcantly different between BTX group and placebo, nor between responders and non-responders. Twenty-seven patients reported minor side-effects, 15 in the botulinum toxin group and 12 in the placebo group. The main complaint was ‘‘short-lasting pain at the injection sites’’. Discussion Our study could not demonstrate botulinum toxin to be more effective than placebo in treatment of neck pain in patients with chronic whiplash syndrome. Previous open label studies with botulinum toxin in patients with chronic whiplash syndrome suggested some beneﬁcial effect on neck pain [12]. Our study is the second published randomized-controlled trial to determine efﬁcacy of botulinum toxin in patients with chronic whiplash syndrome. The other randomized placebo-controlled trial in 26 patients with chronic whiplash syndrome reported a beneﬁcial effect of botulinum toxin [7, 8]. This study, however, has some methodological shortcomings. Primary outcome was improvement of headache intensity scored on the VAS after 4 weeks compared with baseline. The post treatment differ- ence between the two treatment groups was reported to be signiﬁcant. However, baseline-characteristics were signiﬁcantly different, with a signiﬁcant higher headache intensity in the botulinum group at base- line. (VAS 6.5 (range 2–9) versus 3.0 (0–8) in the placebo group (p < 0.01)). The reported improve- ment may mainly have been caused by the unequal distribution of the patients at baseline. In their second publication ( on the same trial) the mean total pain score was reported, ranging from 0–30, expressing the total pain experience for neck pain, headache and shoulder pain. After 4 weeks the mean total pain was 10.0 (SE 1.3) in the botulinum group and 14.1(SE 21) in the placebo group, which was also reported to be signiﬁcant. These data are difﬁcult to interpret with- out individual scores. Calculation of the standard deviation could suggest that some patients even had a negative mean total pain score. In any case, the dis- tribution was truncated and skew to the right. There are some points of discussion in our study. We used injections at trigger points on an individual basis, instead of following a standardized protocol. This might seem subjective and arbitrary, but re- sembles clinical practice and is usually recommended for botulinum toxin (BTX) treatment in pain syn- dromes [10, 16]. We used doses of 100 U Botox , which should be sufﬁcient for a single treatment session. There was only slight, not signiﬁcant, im- provement of cervical range of motion in the botuli- num group, suggesting some, if any, effect on muscle tenderness. Also, none of our patients reported muscular weakness as a side effect. Therefore, further increase of the dosage of botulinum toxin might be possible. There is some evidence that multiple treat- ment sessions are needed for sufﬁcient clinical beneﬁt [20]. In our study there was not even a trend for a positive treatment effect after this single treatment session of BTX. Still, a positive effect of multiple treatment injections cannot be entirely ruled out [16]. Pathophysiology of chronic pain in whiplash syn- drome is still a matter of debate. There is evidence that myofascial pain is a major factor in chronic pain syndromes like chronic neck pain and chronic ten- sion-type headache [14]. The hypothesis of BTX being effective in chronic whiplash syndrome could be pain reduction by decreasing muscle tenderness and/or activity. If increased muscle tenderness is a key fea- ture in chronic neck pain after a whiplash injury, a more beneﬁcial effect of BTX would have been ex- pected. However, in other chronic pain syndromes where muscle tenderness is thought to play a role BTX was also proven ineffective [17, 23]. BTX might only be effective in neck pain in combination with cervical dystonia [26]. In our study were no patients with cervical dystonia.