Evidence map›Paper›PMID 40878124›Full record

ArticleEuropean journal of pain (London, England)2025

Sex Differences in the Effects of Early Life Stressors in a Rat Model of Myofascial Low Back Pain.

Deepika Singhal, Lin Li, Wolfgang Greffrath, Rolf-Detlef Treede

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Article in European journal of pain (London, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Deepika SinghalDepartment of Neurophysiology, Mannheim Centre for Translational Neuroscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.ORCID https://orcid.org/0009-0004-5962-3613
Lin LiDepartment of Neurophysiology, Mannheim Centre for Translational Neuroscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Wolfgang GreffrathDepartment of Neurophysiology, Mannheim Centre for Translational Neuroscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Rolf-Detlef TreedeDepartment of Neurophysiology, Mannheim Centre for Translational Neuroscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundChronic primary low back pain (cpLBP) is prevalent worldwide. Adverse childhood experiences (ACEs) increase the risk of cpLBP. Here, we explored ACEs as a predisposing factor for adult cpLBP using a rodent model.

methodsDuring adolescence, male and female Wistar rats underwent repeated restraint stress (RS) for one hour daily for 12 days or social isolation (SI) for 29 days; controls were handled daily. In adulthood, acute cpLBP was mimicked by NGF or saline injections into the lumbar multifidus muscle. Deep muscular hypersensitivity was assessed using the pressure pain threshold (PPT) of multifidus (MF) and gastrocnemius muscles (GS). Cutaneous mechanical hypersensitivity was measured with paw withdrawal threshold (PWT).

resultsSI had smaller effects than RS in adolescence (d = -0.87 vs. -1.20) and adulthood (d = -0.33 vs. -0.48). RS and SI had a moderate impact in adolescent females (Cohen's d = -0.69), while males experienced a strong sensitisation (d = -1.42), with persistence into adulthood only in males (d = -0.52). Sensitivity to change was lower for PPT of GS (d = -0.71) than PPT of MF (d = -1.09) or PWT (d = -1.17). PPT of the injected MF dropped in stressed females both to saline (d = -0.447) and NGF (d = -0.568) but not in males. Both early life stress models induced immediate muscular and cutaneous hypersensitivity that recovered partly in adulthood.

conclusionsMales were more susceptible to manifest sensitisation by stress than females, whereas females exhibited a memory trace (latent sensitisation), causing hyperalgesia upon the second hit in adulthood. The differential stress sensitivity may contribute to the higher prevalence of cpLBP in females. SIGNIFICANCE STATEMENT: Chronic primary low back pain (cpLBP) is prevalent worldwide, particularly in women. Adverse childhood experiences (ACEs) increase the risk of cpLBP. Using a rat model of cpLBP and two early life stressors, we report that male rats were more susceptible to manifest sensitisation by stress, whereas female rats exhibited a memory trace, causing behavioural signs of hyperalgesia upon the second hit in adulthood (noxious muscle stimulation). The differential stress sensitivity may contribute to the higher prevalence of cpLBP in women.

Indexed as

Low Back PainMyofascial Pain SyndromesSex FactorsStress, PsychologicalAnimalsDisease Models, AnimalFemaleHyperalgesiaMaleMuscle, SkeletalNerve Growth FactorPain ThresholdRatsRats, WistarSocial IsolationNerve Growth Factorchronic primary musculoskeletal painmechanical hyperalgesiamechanical hypersensitivitymyofascial painnerve‐growth factorpaw withdrawal thresholdpressure pain thresholdstrain differences

Identifiers

PMID40878124
PMCPMC12394926

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.