355: Describing Insensitivity and Indifference to Pain: A Scoping Review

Topic: Clinical Science
Subtopic: Non-specific to any diagnosis, Pain in Special Populations , Pain in special populations (e.g. neonates, children, teens, elderly, neurodegenerative diseases)

Background and Aims: Pain insensitivity describes the lack of sensation of pain, while pain indifference describes the perception of a painful stimuli, without the affective response [1]. These two conditions highlight that for most individuals, pain is “an unpleasant sensory and emotional experience” and “pain and nociception are different phenomena” [2]. However, individuals with assumed congenital insensitivity pain, on clinical examination, may have unimpaired sensory responses. As Weisman et al. (2019) highlight, the term “insensitivity to pain conflates pain with nociception” [3]. Because these conditions may impact both longevity and quality of life, a comprehensive literature review is warranted.

Methods: The scoping review process [4] followed the PRISMA guidelines [5]. We searched 5 online databases: PubMed, Embase, Web of Science, CINAHL, and Cochrane. The selection of articles was made through the following search string: ("insensitivity to pain" OR "indifference to pain" OR "pure analgesia" OR "insensitiveness to pain" OR "absence of pain" OR "autonomic neuropathy" OR "sensory neuropathy" OR "asymbolia for pain" OR "pain asymbolia" OR "pain insensitivity" OR "pain indifference" OR analgesia) AND (congenital OR hereditary OR "channelopathy associated"). Articles were screened by title, abstract and full text.

Results: References (16,720) published from inception to July 31, 2025 were identified. After removal of duplicates, 7,469 titles or abstracts were screened, leaving 4,200 articles requiring full-text review. To date (February 15, 2025), 725 were retained for data extraction. Preliminary data extraction from 100 articles revealed diagnostic heterogeneity (e.g. congenital analgesia, congenital insensitivity to pain (with anhidrosis), congenital (universal) indifference to pain, hereditary sensory (and autonomic) neuropathy). Also reported are hereditary complete to progressive sensory loss, and associations to primary diseases (e.g. Charcot Marie Tooth) or genetic variants (e.g. TrkA, NTRK1, SCN9A, SPTLC1, PRDM12).

Conclusions: With congenital insensitivity and indifference to pain attracting medical and pharmaceutical attention, systematic reviews have been conducted on specific topics such as congenital insensitivity to pain and anhidrosis [6, 7], or linked to a loss-of-function mutation in SCN9A [8]. This scoping review will provide an update to the most recent topical review conducted over 20 years ago [1], and map the existing literature on the description of insensitivity and indifference to pain, identify knowledge gaps, and inform directions for future research and inclusion criteria for recruitment of individuals with insensitivity/indifference to pain.

References: 1. Nagasako, E.M., A.L. Oaklander, and R.H. Dworkin, Congenital insensitivity to pain: an update. Pain, 2003. 101(3): p. 213-219.
2. Raja, S.N., et al., The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises. Pain, 2020. 161(9): p. 1976-1982.
3. Weisman, A., J. Quintner, and Y. Masharawi, Congenital Insensitivity to Pain: A Misnomer. J Pain, 2019. 20(9): p. 1011-1014.
4. Ocay, D.D., et al. Congenital Insensitivity and Indifference to Pain: A Scoping Review Protocol. 2025; Available from: osf.io/tfd5b.
5. Tricco, A.C., et al., PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann Intern Med, 2018. 169(7): p. 467-473.
6. Perez-Lopez, L.M., et al., Update Review and Clinical Presentation in Congenital Insensitivity to Pain and Anhidrosis. Case Rep Pediatr, 2015. 2015: p. 589852.
7. Rodriguez-Blanque, R., et al., A Systematic Review of Congenital Insensitivity to Pain, a Rare Disease. J Pers Med, 2024. 14(6).
8. Peddareddygari, L.R., K. Oberoi, and R.P. Grewal, Congenital insensitivity to pain: a case report and review of the literature. Case Rep Neurol Med, 2014. 2014: p. 141953.

Presenting Author: Don Daniel Ocay
Submitting Author: Don Daniel Ocay

Senior Author: Charles Berde

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Don Daniel Ocay - Boston Children's Hospital
• Rita Ouldsahraouia - Boston Children's Hospital
• Jean Solodiuk - Boston Children's Hospital
• Charles Berde - Boston Children's Hospital