Phenotyping nociceptive, neuropathic, and nociplastic pain in the past, present and future   May 30th, 2024

Do you consider all myofascial pain to be nociceptive pain? Do you consider all carpal tunnel syndrome and/or all post-chemotherapy pain pure neuropathic pain? Do you explain pain in the same way to patients with nociceptive, neuropathic, and nociceptive pain?1 If you respond positively to at least one of these questions, we invite you to continue reading. You see, phenotyping persistent pain into predominantly nociceptive, neuropathic or nociplastic pain is not that straightforward and potentially, pain phenotyping has clinical implications.

Yet, pain phenotyping has come a long way, with initial attempts dating back to 20102,3, long before the term ‘nociplastic pain’ was introduced by the International Association for the Study of Pain (IASP). Back then, a ‘masterclass’ paper described a first attempt for supporting clinicians in their clinical reasoning process to recognize central sensitization in patients with chronic musculoskeletal pain3, but the first structured approach to pain phenotyping in clinical practice was an expert consensus-derived list of clinical criteria suggestive of a clinical dominance of nociceptive, peripheral neuropathic and 'central' mechanisms of musculoskeletal pain.2

Nowadays, the IASP clinical criteria and a grading system for nociplastic pain affecting the musculoskeletal system4, which integrates the neuropathic pain criteria5, represents the ‘gold standard’. These IASP clinical criteria for pain phenotyping have been applied to a variety of complex pain disorders. This is done to recognize the complexity of many specific pain disorders, such as low back pain6 and post-cancer pain7, and to support researchers and clinicians in applying the pain phenotyping criteria in a ‘disease-specific’ manner. Below an overview of the current pain phenotyping criteria, applied to specific conditions, is provided including the (often open access) full-text link.

Kosek E, Clauw D, Nijs J, Baron R, Gilron I, Harris RE, Mico JA, Rice ASC, Sterling M. Chronic nociplastic pain affecting the musculoskeletal system: clinical criteria and grading system. Pain. 2021;162(11):2629-2634. 

https://journals.lww.com/pain/fulltext/2021/11000/chronic_nociplastic_pain_affecting_the.4.aspx

Nijs J, Lahousse A, Kapreli E, Bilika P, Saraçoğlu İ, Malfliet A, Coppieters I, De Baets L, Leysen L, Roose E, Clark J, Voogt L, Huysmans E. Nociplastic Pain Criteria or Recognition of Central Sensitization? Pain Phenotyping in the Past, Present and Future. J Clin Med. 2021;10(15):3203. https://www.mdpi.com/2077-0383/10/15/3203

LOW BACK PAIN:

Nijs J, Kosek E, Chiarotto A, Cook C, Danneels LA, Fernández-de-Las-Peñas C, Hodges PW, Koes B, Louw A, Ostelo R, Scholten-Peeters GGM, Sterling M, Alkassabi O, Alsobayel H, Beales D, Bilika P, Clark JR, De Baets L, Demoulin C, de Zoete RMJ, Elma Ö, Gutke A, Hanafi R, Hotz Boendermaker S, Huysmans E, Kapreli E, Lundberg M, Malfliet A, Meziat Filho N, Reis FJJ, Voogt L, Zimney K, Smeets R, Morlion B, de Vlam K, George SZ. Nociceptive, neuropathic, or nociplastic low back pain? The low back pain phenotyping (BACPAP) consortium's international and multidisciplinary consensus recommendations. Lancet Rheumatol. 2024;6(3):e178-e188.

https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(23)00324-7/abstract

POST-CANCER PAIN:

Nijs J, Lahousse A, Fernández-de-Las-Peñas C, Madeleine P, Fontaine C, Nishigami T, Desmedt C, Vanhoeij M, Mostaqim K, Cuesta-Vargas AI, Kapreli E, Bilika P, Polli A, Leysen L, Elma Ö, Roose E, Rheel E, Yılmaz ST, De Baets L, Huysmans E, Turk A, Saraçoğlu İ. Towards precision pain medicine for pain after cancer: the Cancer Pain Phenotyping Network multidisciplinary international guidelines for pain phenotyping using nociplastic pain criteria. Br J Anaesth. 2023;130(5):611-621.

https://www.bjanaesthesia.org/article/S0007-0912(22)00738-3/fulltext

Editorial comment on the cancer pain phenotyping criteria:

Verspyck E, Attal N. Diagnosing nociplastic pain in cancer survivors: a major step forward. Br J Anaesth. 2023;130(5):515-518.

https://www.bjanaesthesia.org/article/S0007-0912(23)00064-8/abstract

POST-COVID PAIN:

Fernández-de-Las-Peñas C, Nijs J, Neblett R, Polli A, Moens M, Goudman L, Shekhar Patil M, Knaggs RD, Pickering G, Arendt-Nielsen L. Phenotyping Post-COVID Pain as a Nociceptive, Neuropathic, or Nociplastic Pain Condition. Biomedicines. 2022;10(10):2562.

https://www.mdpi.com/2227-9059/10/10/2562

Fernández-de-Las-Peñas C, Nijs J, Giordano R, Arendt-Nielsen L. Precision management of post-COVID pain: An evidence and clinical-based approach. Eur J Pain. 2023;27(9):1107-1125. https://onlinelibrary.wiley.com/doi/10.1002/ejp.20...

MYOFASCIAL PAIN:

Fernández-de-Las-Peñas C, Nijs J, Cagnie B, Gerwin RD, Plaza-Manzano G, Valera-Calero JA, Arendt-Nielsen L. Myofascial Pain Syndrome: A Nociceptive Condition Comorbid with Neuropathic or Nociplastic Pain. Life (Basel). 2023;13(3):694.https://www.mdpi.com/2075-1729/13/3/694

CARPAL TUNNEL SYNDROME:

Fernández-de-Las-Peñas C, Fuensalida-Novo S, Nijs J, Basson A, Plaza-Manzano G, Valera-Calero JA, Arendt-Nielsen L, de-la-Llave-Rincón AI. Carpal Tunnel Syndrome: Neuropathic Pain Associated or Not with a Nociplastic Condition. Biomedicines. 2023;11(6):1744.

https://www.mdpi.com/2227-9059/11/6/1744

SHOULDER PAIN:

Submitted for publication.

FIBROMYALGIA:

In progress.

Obviously, pain phenotyping is a work in progress. Within the IASP Terminology Task Force, we are working hard to optimize the current ‘gold standard’ criteria. At the University of Thessaly (Lamia, Greece), Professor Eleni Kapreli and Dr. Paraskevi Bilika have been, and are conducting rigorous reliability and validity testing of the IASP pain phenotyping criteria. Taken together, this is an exciting area for pain researchers and clinicians, continuing to attract international attention.

Jo Nijs1,2,3

1 Pain in Motion Research Group (PAIN), Department of Physical therapy, Human Physiology and Anatomy, Faculty of Physical Education & Physical therapy, Vrije Universiteit Brussel, Belgium

2Chronic pain rehabilitation, Department of Physical Medicine and Physical therapy, University Hospital Brussels, Belgium

3 Department of Health and Rehabilitation, Unit of Physical therapy, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden

References

1. Nijs J, De Baets L, Hodges P. Phenotyping nociceptive, neuropathic, and nociplastic pain: who, how, & why? Braz J Phys Ther 2023; 27(4): 100537.

2. Smart KM, Blake C, Staines A, Doody C. Clinical indicators of 'nociceptive', 'peripheral neuropathic' and 'central' mechanisms of musculoskeletal pain. A Delphi survey of expert clinicians. Manual therapy 2010; 15(1): 80-7.

3. Nijs J, Van Houdenhove B, Oostendorp RA. Recognition of central sensitization in patients with musculoskeletal pain: Application of pain neurophysiology in manual therapy practice. Manual therapy 2010; 15(2): 135-41.

4. Kosek E, Clauw D, Nijs J, Baron R, Gilron I, Harris RE, Mico JA, Rice ASC, Sterling M. Chronic nociplastic pain affecting the musculoskeletal system: clinical criteria and grading system. Pain 2021; 162(11): 2629-34.

5. Finnerup NB, Haroutounian S, Kamerman P, Baron R, Bennett DLH, Bouhassira D, Cruccu G, Freeman R, Hansson P, Nurmikko T, Raja SN, Rice ASC, Serra J, Smith BH, Treede RD, Jensen TS. Neuropathic pain: an updated grading system for research and clinical practice. Pain 2016; 157(8): 1599-606.

6. Nijs J, Kosek E, Chiarotto A, Cook C, Danneels LA, Fernández-de-Las-Peñas C, Hodges PW, Koes B, Louw A, Ostelo R, Scholten-Peeters GGM, Sterling M, Alkassabi O, Alsobayel H, Beales D, Bilika P, Clark JR, De Baets L, Demoulin C, de Zoete RMJ, Elma Ö, Gutke A, Hanafi R, Hotz Boendermaker S, Huysmans E, Kapreli E, Lundberg M, Malfliet A, Meziat Filho N, Reis FJJ, Voogt L, Zimney K, Smeets R, Morlion B, de Vlam K, George SZ. Nociceptive, neuropathic, or nociplastic low back pain? The low back pain phenotyping (BACPAP) consortium's international and multidisciplinary consensus recommendations. Lancet Rheumatol 2024; 6(3): e178-e88.

7. Nijs J, Lahousse A, Fernández-de-Las-Peñas C, Madeleine P, Fontaine C, Nishigami T, Desmedt C, Vanhoeij M, Mostaqim K, Cuesta-Vargas AI, Kapreli E, Bilika P, Polli A, Leysen L, Elma Ö, Roose E, Rheel E, Yılmaz ST, De Baets L, Huysmans E, Turk A, Saraçoğlu İ. Towards precision pain medicine for pain after cancer: the Cancer Pain Phenotyping Network multidisciplinary international guidelines for pain phenotyping using nociplastic pain criteria. British journal of anaesthesia 2023; 130(5): 611-21.