294 the sensitivity of high-threshold nociceptors (per- ipheral sensitization). This, in turn, sets up changes in the responsiveness of neurons in the central nervous system (CNS), ultimately increasing the excitability of neurons within the CNS, representing central sensitization [21]. Patients with chronic whiplash syndrome display exaggerated pain after sensory sti- mulation as a consequence of this state of hyper- excitability of the central nociceptive system [1, 13]. In other words, an alteration in function of the central nervous system, the way it responds to normal inputs, seems present in these patients. This central hypersensivity is probably in- dependent of the nociceptive input arising from the painful and tender muscles [4], and possibly a con- sequence of deﬁcient pain inhibitory systems. Many somatic, psychological or cultural factors may inﬂuence central sensitization. Different studies show that prognosis of chronic whiplash syndrome is also dependent on cultural factors [15, 18, 22]. It has even been shown that presence or absence of com- pensation claims is one of the most important pre- dictors of bad outcome in patients after whiplash injury (also present in our group in 75–90% of the patients) [11, 19]. The etiological contribution of all different psychological factors, like for example cop- ing style [3], to central sensitization is not yet clar- iﬁed. It is not to be predicted that BTX will improve all different factors, especially psychological and cul- tural factors, which may contribute to development of this chronic whiplash syndrome. Based on present evidence BTX cannot be re- commended as treatment for neck pain in chronic whiplash patients. Future studies directed on possible central mechanisms of this complicated chronic pain syndrome are warranted. j Contributors The trial was designed by S.F.T.M. de Bruijn, D.L.J. Tavy and M. Padberg. Statistical analysis was per- formed by M. Padberg. Conflict of interest statement Non declared. j Acknowledgement Appreciation is expressed to N. van der Lubbe and A. Heering (department physical therapy), R.J. de Haan and R. Wolterbeek for their statistical advices. To D. Janssen for her assistance in data collection. Allergan provided the study medica- tion, but was not involved in the collection, analysis and inter- pretation of the data. This trial was supported by a financial grant from the Dr. Eduard Hoelen Foundation at The Hague. References 1. Banic B, Petersen-Felix S, Andersen OK, Radanov BP, Villiger PM, Arendt- Nielsen L, Curatolo M (2004) Evidence for spinal cord hypersensivity in chronic pain after whiplash injury and in ﬁbromyalgia. Pain 107:7–15 2. Barnsley L (2000) Epidemiology of whiplash. Ann Rheum Dis 59:394–396 3. Buitenhuis J, Spanjer J, Fidler V (2003) Recovery from acute whiplash: the role of coping styles. Spine 28:896–901 4. Curatolo M, Petersen-Felix S, Arendt- Nielsen L, Giani C, Zbinden AM, Ra- danov BP (2001) Central hypersensi- tivity in chronic pain after whiplash injury. Clin J Pain 17:306–315 5. Davidoff RA (1998) Trigger points and myofascial pain: toward understanding how they affect headaches. Cephalalgia 18:436–448 6. Freund BJ, Schwartz M (1999) Treat- ment of whiplash associated neck pain with botulinum toxin-A: report of 8 cases. J Rheumatol 26:756–758 7. Freund BJ, Schwartz M (2000) Treat- ment of chronic cervical-associated headache with botulinum toxin A: a pilot study. Headache 40:231–236 8. Freund BJ, Schwartz M (2000) Treat- ment of whiplash associated neck pain [corrected] with botulinum toxin-A: a pilot study. J Rheumatol 27:481–484 9. Frymoyer JW (1991) The Adult Spine: Principles and Practices: 1st Edition. In: Raven Press, Ltd., New York, pp 172– 177 10. Gobel H, Heinze A, Heinze-Kuhn K, Jost WH (2001) Evidence-based medi- cine: botulinum toxin A in migraine and tension-type headache. J Neurol 248(Suppl 1):34–38 11. Hendriks EJ, Scholten-Peeters GG, van der Windt DA, Neeleman-van der Steen CW, Oostendorp RA, Verhagen AP (2005) Prognostic factors for poor re- covery in acute whiplash patients. Pain 114:408–416 12. Juan FJ (2003) Treatment of neck pain after whiplash injuries with botulinum toxin-A injections. J Musculoskel Res 7(3 & 4):221–223 13. Koelbaek JM, Graven-Nielsen T, Schou OA, Arendt-Nielsen L (1999) General- ised muscular hyperalgesia in chronic whiplash syndrome. Pain 83:229–234 14. Mork H, Ashina M, Bendtsen L, Olesen J, Jensen R (2004) Possible mechanisms of pain perception in patients with episodic tension-type headache. A new experimetal model of myofascial pain. Cephalalgia 24:466–475 15. Obelieniene D, Schrader H, Bovim G, Miseviciene I, Sand T (1999) Pain after whiplash: a prospective controlled in- ception cohort study. J Neurol Neuro- surg Psychiatry 66:279–283 16. Ondo WG, Vuong KD, Derman HS (2004) Botulinum toxin A for chronic daily headache: a randomized, placebo- controlled, parallel design study. Ce- phalalgia 24:60–65 17. Padberg M, Bruijn de SFTM, Haan de RJ, Tavy DLJ (2004) Treatment of chronic tension-type headache with botulinum toxin: a double-blind, pla- cebo-controlled clinical trial. Cepha- lalgia 24:675–680