Decreased pain sensitivity among people with schizophrenia: a meta-analysis of experimental pain induction studies
Open accessAbstract
Patients with schizophrenia report reduced pain sensitivity in clinical studies, but experimental studies are required to establish pain sensitivity as a potential endophenotype. We conducted a systematic review of electronic databases from database inception until April 15, 2015, including experimental studies investigating pain among patients with schizophrenia spectrum disorder vs healthy controls. A random-effect meta-analysis yielding Hedges' g ±95% confidence intervals (CIs) as the effect size (ES) measure was conducted. Primary outcome was a pooled composite of pain threshold and pain tolerance; secondary outcomes included these parameters individually, plus sensory threshold, physiological pain response, and pain intensity or unpleasantness. Across 17 studies, patients with schizophrenia spectrum disorder (n = 387; age, 30.7 ± 6.9 years; females, 31.9%; illness duration, 7.0 ± 5.7 years) were compared with controls (n = 483; age, 29.5 ± 7.4 years; females, 31.0%). Patients had elevated pain threshold/pain tolerance vs controls (ES = 0.583; 95% CI, 0.212-0.954; P = 0.002; studies = 15). Results were similar in antipsychotic-free individuals (ES = 0.599; 95% CI, 0.291-0.907; P < 0.0001; studies = 8), with trend-level significance in antipsychotic-treated individuals (ES = 0.566; 95% CI, -0.007 to 1.125; P = 0.047; studies = 9). Likewise, patients with schizophrenia had increased pain tolerance (ES = 0.566; 95% CI, 0.235-0.897; P = 0.0001; studies = 6), sensory threshold (ES = 1.16; 95% CI, 0.505-1.727; P < 0.0001; studies = 5), and pain threshold (ES = 0.696; 95% CI, 0.407-0.986; P < 0.001; studies = 9), as well as reduced physiological response to noxious stimuli (ES = 0.456; 95% CI, 0.131-0.783; P = 0.006) and pain intensity/unpleasantness ratings (ES = 0.547; 95% CI, 0.146-0.949; P = 0.008). Findings were similarly significant in antipsychotic-free patients with schizophrenia (analysable parameters = 4) and antipsychotic-treated individuals (analysable parameters = 2). Finally, greater psychiatric symptoms moderated increased pain threshold, and younger patient age moderated increased pain tolerance. Decreased pain sensitivity seems to be an endophenotype of schizophrenia spectrum disorders. How this alteration links to other dimensions of schizophrenia and physical comorbidity-related help-seeking behaviour/morbidity/mortality requires further study.
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Hyper- and hypo-sensitivity to pain have been reported in depression, schizophrenia, eating disorders, autism, and OCD.
“Beyond sensory responsiveness in developmental disorders, hyper- and hypo-sensitivity to pain have been reported in a number of clinical populations, such as depression (Hermesdorf et al., 2016), schizophrenia (Stubbs et al., 2015), eating disorders (Papezová et al., 2005; Yamamotova et al., 2017), autism (Riquelme et al., 2016), and OCD (Hezel et al., 2012).”
From Atypical interoception as a common risk factor for psychopathology: A review (2021) · cites this paper as Stubbs et al., 2015
The Discussion (page not supplied) reports hypoalgesia in people with schizophrenia, supporting the hypo-sensitivity part of the schizophrenia citation. The paper’s findings do not establish hyper-sensitivity in this population; a hypersensitivity study appears only in the References. The other conditions in the sentence have separate citations and are not attributed to this source. (LLM, conf=0.83)
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- Authors
- Stubbs, B., Thompson, T., Acaster, S., Vancampfort, D., Gaughran, F., & Correll, C. U.
- Affiliations
- National Health Service (GB)
- University of Greenwich (GB)
- KU Leuven (BE)
- South London and Maudsley NHS Foundation Trust (GB)
- Long Island Jewish Medical Center (US)
- Corresponding author
- Stubbs, Brendon
- ORCID
- Venue
- Pain
- Published
- 2015-11
- Volume
- 156
- Issue
- 11
- Pages
- 2121-2131
- ISSN
- 0304-3959 (ISSN-L)
- OpenAlex
- W994897398
- Cited by
- 141
- References
- 49
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 22 · 2023: 8 · 2022: 15 · 2021: 15 · 2020: 10 · 2019: 12 · 2018: 9 · 2017: 15 · 2016: 10 · 2015: 1
- FWCI
- 1.60
- Type
- journal article
- Language
- en
- Open access
- green
- kclpure.kcl.ac.uk
- Licence
- other-oa
- Locations
- Pain (publishedVersion)
- PubMed (publishedVersion)
- Greenwich Academic Literature Archive (University of Greenwich) (acceptedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Lirias (KU Leuven) (submittedVersion)
- Funders
- Bristol-Myers Squibb
- Sunovion
- H. Lundbeck A/S
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Keywords
- schizophrenia, schizophrenia spectrum disorders, pain sensitivity, pain threshold, pain tolerance, endophenotypes, sensory threshold, antipsychotic drugs, physiological pain response, pain unpleasantness, pain intensity, antipsychotic adverse effects
- MeSH terms
- Adult, Female, Humans, Male, Pain, Physical Stimulation, Schizophrenia, Databases, Factual, Pain Threshold, Young Adult
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