on Jan 4th, 2019

Neck pain represents one of the most frequent musculoskeletal disorders, with a huge impact in terms of health-care costs and it is the fourth leading cause of disability (Hoy et al., 2014).

Central sensitization is a phenomenon which is commonly found in whiplash subjects (WAD). Although in some individuals with mechanical neck pain (MNP) this condition may exist (Javanshir et al., 2010Johnston et al., 2008), for most it does not seems to be a main feature (Malfliet et al., 2015Coppieters et al., 2015). Recently, 4 sub-groups of neck pain subjects (mixed sample of traumatic and mechanical neck pain subjects) have been identified, and the biggest group (67% of the total sample) showed signs of central sensitization (i.e. lowered pressure pain thresholds (PPTs) both locally and widespread) (Walton et al., 2017). However, the clinical presentation may be very heterogenous, as found in my PhD project:we found higher signs of central sensitization in WAD subjects in one study, while in two other studies we did not find a difference between the two neck pain groups(Castaldo et al., 2018Castaldo et al., 2017; Castaldo et al., submitted).

From a preliminary RCT it is shown that a higher degree of central sensitization may limit the outcome of rehabilitation(Jull et al., 2007), and could partially explain the large amount of subjects suffering from ongoing pain after the first neck pain episode (Carroll et al., 2008). As clinicians we must consider the presence of central sensitization in our patients with neck pain, as they need a different therapeutic approach.

A peripheral nociceptive input (injury, overload, inflammation) seems to be responsible for initiating/maintaining the central nervous system hypersensitivity (Baron et al., 2013). One explanation might be the presence of active Triggerpoints (TrPs), which were more common in WAD subjects (Castaldo et al., 2014). Furthermore, our study showed that subjects (from both groups) with active TrPs in the upper trapezius muscle had lowered PPTs compared with subjects with only latent TrPs in the same muscle (Castaldo et al., 2018). Unfortunately, there is still a lack of diagnostic gold standard for TrPs (Srbely et al., 2016). A recent systematic review concluded that the reliability of manual palpation is low, and that future investigation should focus on integration with more reliable techniques (Rathbone et al., 2017). However, the results from our study show that there might be some evidence to support the role of TrPs (particularly active TrPs) as source of peripheral nociception, which may over time increase the barrage to the central nervous system, and can finally increase excitability and synaptic efficacy of neurons in central nociceptive pathways (Nystrom and Freeman, 2017Mense and Gerwin, 2010).

The management of central sensitization requires a multidisciplinary approach, as treatment of the peripheral nociceptive input (i.e. TrPs) may not be sufficient to reverse this phenomenon: this is confirmed by our results, with an improvement in pain, ROM and disability with manual therapy and exercise (in both neck pain populations), but without a significant improvement in widespread PPTs levels (Castaldo et al., 2017). This seem to confirm that PPTs are only partially related to day-to-day pain and disability experience of the subjects, and other factors (e.g. psychological status, pain duration, health status) must play a role (Kamper et al., 2011). Further, probably TrPs and PPTs capture only a part of the sensitization process, and other assessments (e.g. thermal thresholds, nociceptive flexion withdrawal reflex) may provide a more robust measure of central hyperexcitability.

We found that pain duration and general health status showed significant correlations with PPTs: the longer the health condition (i.e. medical conditions, other musculoskeletal pain, surgical operations, constant medication intake)were present, the lower were the local and widespread PPTs (Castaldo et al., submitted). These findings support the role of time in the development and progression of central nervous system hypersensitivity. Which was also found in recent studies wherein associations between pain duration and PPTs levels were found. However, the time necessary to this progressive sensitization is still unclear (Fernández-de-Las-Peñas et al., 2017Arendt-Nielsen et al., 2015). This support the importance of investigating the presence of prior pain conditions, abnormal disease course, and the general medical condition (Nijs et al., 2010), which may all be helpful in the identification of central sensitization in the clinical setting. Whereby, the idenfitication of the duration of complaints may be particularly important in MNP subjects. In WAD subjects signs of central sensitization already develop in the first month after the trauma (Sterling et al., 2003), while in MNP it may need more time to develop, being usually more episodic in nature (Haldeman et al., 2008). Previously signs of central sensitization have been found only in chronic MNP subjects (Javanshir et al., 2010Johnston et al., 2008), suggesting that it may take longer to develop in subjects affected by this pain condition.

To conclude, different factors (e.g. pain duration, health status, peripheral input, psychological aspects) must be considered in patients with neck pain, as a better profiling of these patients according to the central sensitization level is needed, in order to improve the treatment efficacy, and to reduce the chronicity of these pain conditions.

Matteo Castaldo

Matteo Castaldo is a physiotherapist from Italy, who has recently completed a PhD at Aalborg University (Denmark), with the title “Sensitization in neck pain: a comparison between whiplash-associated disorders and mechanical neck pain subjects”. He is currently working at Aalborg University as a part-time post doc, focusing on a project on headache and central sensitization. Furthermore, he is working clinically with neck pain and headache patients in Parma (Italy) at his clinic. His teaching activities comprise of teaching both private courses and as a lecturer at University of Parma and University of Siena.

2018 Pain in Motion

References and further reading:

Arendt-Nielsen, L., Egsgaard, L.L., Petersen, K.K., Eskehave, T.N., Graven-Nielsen, T., Hoeck, H.C., & Simonsen, O. (2015). A mechanism-based pain sensitivity index to characterize knee osteoarthritis patients with different disease stages and pain levels. European Journal of Pain,19(10), 1406–1417.


Baron, R., Hans, G., & Dickenson, A. H. (2013). Peripheral Input and Its Importance for Central Sensitization. Annals of Neurology, 74(5):630-636. https://www.ncbi.nlm.nih.gov/pubmed/24018757

Carroll, L. J., Hogg-Johnson, S., Côté, P., van der Velde, G., Holm, L. W., Carragee, E. J., … Haldeman, S. (2008). Course and Prognostic Factors for Neck Pain in Workers. European Spine Journal, 17(S1), 93–100. https://www.ncbi.nlm.nih.gov/pubmed/18204406


Castaldo MGe HYChiarotto AVillafane JHArendt-Nielsen L. Myofascial trigger points in patients with whiplash-associated disorders and mechanical neck pain. Pain Med 2014;15(5):842-9. https://www.ncbi.nlm.nih.gov/pubmed/24641263

Castaldo M, Catena A, Chiarotto A, Fernández-de-Las-Peñas C, Arendt-Nielsen L. Do Subjects with Whiplash-Associated Disorders Respond Differently in the Short-Term to Manual Therapy and Exercise than Those with Mechanical Neck Pain? Pain Med 2017; 18 (4): 791-803 https://www.ncbi.nlm.nih.gov/pubmed/28034987

Castaldo M, Catena A, Chiarotto A, Villafañe JH, Fernández-de-las-Peñas C, Arendt-Nielsen L. Association between Clinical and Neurophysiological Outcomes in Patients with Mechanical Neck Pain and Whiplash-associated Disorders. Clin J Pain. 2018 Feb;34(2):95-103https://www.ncbi.nlm.nih.gov/pubmed/28678060

Castaldo M, Catena A, Fernández-de-las-Peñas C, Arendt-Nielsen L. Widespread pressure pain hypersensitivity, health history, and trigger points in patients with mechanical and traumatic neck pain: an explorative study. Submitted

Coppieters, I., Cagnie, B., Danneels, L., Ickmans, K., & Meeus, M. (2015). Central pain modulation and cognitive functioning in patients with traumatic and nontraumatic chronic neck pain: preliminary results. EFIC 2015 Abstracts.


Fernández-de-las-Peñas, C., Benito-González, E., Palacios-Ceña, M., Wang, K., Castaldo, M., & Arendt-Nielsen, L. (2017). Identification of subgroups of patients with tension type headache with higher widespread pressure pain hyperalgesia. The Journal of Headache and Pain, 18(1), 43.


Haldeman, S., Carroll, L., & Cassidy, J. D. (2010). Findings From The Bone and Joint Decade 2000 to 2010 Task Force on Neck Pain and Its Associated Disorders. Journal of Occupational and Environmental Medicine, 52(4), 424–427.



Hoy, D., March, L., Woolf, A., Blyth, F., Brooks, P., Smith, E., … Buchbinder, R. (2014). The global burden of neck pain: estimates from the Global Burden of Disease 2010 study. Annals of the Rheumatic Diseases, 73(7), 1309–1315.


Javanshir, K., Ortega-Santiago, R., Mohseni-Bandpei, M. A., Miangolarra-Page, J. C., & Fernández-de-las-Peñas, C. (2010). Exploration of Somatosensory Impairments in Subjects With Mechanical Idiopathic Neck Pain: A Preliminary Study. Journal of Manipulative and Physiological Therapeutics, 33(7), 493–499.


Johnston, V., Jimmieson, N. L., Jull, G., & Souvlis, T. (2008). Quantitative sensory measures distinguish office workers with varying levels of neck pain and disability. Pain, 137(2), 257–265.


Jull, G., Sterling, M., Kenardy, J., & Beller, E. (2007a). Does the presence of sensory hypersensitivity influence outcomes of physical rehabilitation for chronic whiplash? – A preliminary RCT. Pain, 129(1), 28–34.


Kamper, S. J., Maher, C. G., Hush, J. M., Pedler, A., & Sterling, M. (2011). Relationship Between Pressure Pain Thresholds and Pain Ratings in PatientsWith Whiplash-associated Disorders. The Clinical Journal of Pain, 27(6),495–501.


Malfliet, A., Kregel, J., Cagnie, B., Meeus, M., Danneels, L., Bramer, W. M., & Nijs, J. (2015). Lack of Evidence for Central Sensitization in Idiopathic, Non-Traumatic Neck Pain: A Systematic Review. Pain Physician, 18(3): 223–235.


Mense, S., & Gerwin, R. D. (Eds.). (2010).Muscle pain: understanding the mechanisms. Springer Science & Business Media.https://link.springer.com/content/pdf/bfm%3A978-3-...

Nijs, J., Houdenhove, B. Van, & Oostendorp, R. A. B. (2010). Recognition of central sensitization in patients with musculoskeletal pain: Application of pain neurophysiology in manual therapy practice. Manual Therapy, 15(2), 135–141.


Nystrom, N. A., & Freeman, M. D. (2017). Central Sensitization Is Modulated Following Trigger Point Anesthetization in Patients with Chronic Pain from Whiplash Trauma. A Double-Blind, Placebo-Controlled, Crossover Study.Pain Medicine.



Rathbone, A. T. L., Grosman-Rimon, L., & Kumbhare, D. A. (2017). Interrater Agreement of Manual Palpation for Identification of Myofascial Trigger Points. The Clinical Journal of Pain, 33(8), 715–729.


Srbely, J. Z., Dickey, J. P., Bent, L. R., Lee, D., & Lowerison, M. (2010). Capsaicin. Induced Central Sensitization Evokes Segmental Increases in Trigger Point Sensitivity in Humans. The Journal of Pain, 11(7), 636–643.


Sterling, M., Jull, G., Vicenzino, B., & Kenardy, J. (2003). Sensory hypersensitivity occurs soon after whiplash injury and is associated with poor recovery. Pain,104(3):509–517.


Walton, D.M., Kwok, T. S. H., Mehta, S., Loh, E., Smith, A., Elliott, J., … Sterling, M. (2017). Cluster Analysis of an International Pressure Pain Threshold Database Identifies 4 Meaningful Subgroups of Adults With Mechanical Neck Pain. The Clinical Journal of Pain, 33(5), 422–428. https://www.ncbi.nlm.nih.gov/pubmed/27518490

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