What makes surgical nerve injury painful? A 4-year to 9-year follow-up of patients with intercostobrachial nerve resection in women treated for breast cancer

Mustonen, Laura; Aho, Tommi; Harno, Hanna; Sipilä, Reetta; Meretoja, Tuomo J.; Kalso, Eija

doi:10.1097/j.pain.0000000000001398

Cited by 47 publications

(79 citation statements)

References 46 publications

(67 reference statements)

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“…elsewhere" was evaluated as more interfering than pain in the surgical area. A common finding in similar studies is that previous pains are relevant for the experience of a new pain [48], which was the case also in the present patient cohort [18]. It may be hypothesised that the overall pain load is relevant regarding how interfering the patient experiences her pain.…”

Section: Discussionsupporting

confidence: 75%

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Machine-learned identification of psychological subgroups with relation to pain interference in patients after breast cancer treatments

2020

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Background: Persistent pain in breast cancer survivors is common. Psychological and sleep-related factors modulate perception, interpretation and coping with pain and may contribute to the clinical phenotype. The present analysis pursued the hypothesis that breast cancer survivors form subgroups, based on psychological and sleep-related parameters that are relevant to the impact of pain on the patients' life. Methods: We analysed 337 women treated for breast cancer, in whom psychological and sleep-related parameters as well as parameters related to pain intensity and interference had been acquired. Data were analysed by using supervised and unsupervised machine-learning techniques (i) to detect patient subgroups based on the pattern of psychological or sleep-related parameters, (ii) to interpret the detected cluster structure and (iii) to relate this data structure to pain interference and impact on life. Results: Artificial intelligence-based detection of data structure, implemented as self-organizing neuronal maps, identified two different clusters of patients. A smaller cluster (11.5% of the patients) had comparatively lower resilience, more depressive symptoms and lower extraversion than the other patients. In these patients, life-satisfaction, mood, and life in general were comparatively more impeded by persistent pain. Conclusions: The results support the initial hypothesis that psychological and sleep-related parameter patterns are meaningful for subgrouping patients with respect to how persistent pain after breast cancer treatments interferes with their life. This indicates that management of pain should address more complex features than just pain intensity. Artificial intelligence is a useful tool in the identification of subgroups of patients based on psychological factors.

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Section: Discussionsupporting

confidence: 75%

“…The patients answered the questionnaires during the research visit. The study protocols have been described earlier in detail [17,18]. Information about patient recruitment is provided in Fig.…”

Section: Patients and Data Acquisitionmentioning

confidence: 99%

Machine-learned identification of psychological subgroups with relation to pain interference in patients after breast cancer treatments

2020

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“…No such treatment is currently available (51). Since not all individuals with neural injury develop neuropathic pain, who is at risk and what drives susceptibility are critical missing pieces of information (52,53).…”

Section: Neuropathic Painmentioning

confidence: 99%

Capturing Novel Non-opioid Pain Targets

Woolf

2020

Biological Psychiatry

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The relatively high efficacy of opioids, which have associated risks of addiction, tolerance, and dependence, for the management of acute and terminal pain has been a major driver of the opioid crisis, together with the availability, overprescription, and diversion of these drugs. Eliminating opioids without an effective replacement is, however, no solution, as it substitutes one major problem with another. To deal successfully with the opioid crisis, we need to discover novel analgesics whose mechanisms do not involve the mu opioid receptor but that have high analgesic potency and low risk of adverse effects, particularly no abuse liability. The question is how to achieve this. There are several necessary elements; first, we need to understand the nature of pain and the mechanisms responsible for it, and second, we need to adopt novel and unbiased approaches to the identification and validation of pain targets.

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“…For example, chemokines have been shown to be altered in patients who have had NP for at least 6 months. However, it is possible that changes in human CSF proteomics are associated with comorbidities that predispose to NP [44,45].…”

Section: Csf Proteomicsmentioning

confidence: 99%

Spared nerve injury causes sexually dimorphic mechanical allodynia and differential gene expression in spinal cords and dorsal root ganglia in rats

Ahlström

Mätlik

Viisanen

et al. 2020

Preprint

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BACKGROUND Neuropathic pain (NP) is more prevalent in women. However, females are under-represented in animal experiments, and the mechanisms of sex differences remain inadequately understood. Using the spared nerve injury (SNI) model in rats, we characterized sex differences in behaviour, analysed dorsal root ganglion (DRG) and spinal cord (SC) tissues with transcriptomics and immunohistochemistry assays, and examined the proteome of cerebrospinal fluid (CSF). METHODS The study comprised two experiments, with male and female Sprague-Dawley rats subjected to SNI- and sham-surgeries. Mechanical and cold allodynias were assessed using von Frey filaments and the acetone test, respectively. Samples were extracted on Day 21 for CSF proteome and DRG and SC analysis for neuronal markers (IB4 and CGRP) and glial cell markers (IBA1 and GFAP), respectively, in Experiment I. Lumbar 4-5 DRGs and SC segments were collected for RNA-seq analysis on Day 7 in Experiment II. Differential gene expression in DRG and SC was calculated using DESeq2, and pathway analyses were conducted using iPathwayguide. RESULTS Females developed stronger mechanical allodynia in both experiments. Equivalent decreases in CGRP and IB-4 positive cell counts in DRG and increases in glial cells markers in the SC were seen in both sexes. No CSF protein showed change following SNI in any group. RNASeq of DRG and SC showed abundant changes in gene expression. Sexually dimorphic responses were found in genes related to T-cells (cd28, ctla4, cd274, cd4, prf1), other immunological responses (dpp4, c5a, cxcr2 and il1b), neuronal transmission (hrh3, thbs4, chrna4 and pdyn), plasticity (atf3, c1qc and reg3b), and others (bhlhe22, mcpt1l, trpv6). Analyses of biological processes revealed differences in T and B cell functions in DRG and neuronal processes in both DRG and SC. CONCLUSIONS We observed significantly stronger mechanical allodynia in females and many sexually dimorphic changes in gene expression, following SNI in rats. Several genes have previously been linked to NP, while some are novel. Our results suggest gene targets for further studies in the development of new, possibly sex-specific, therapies for NP and underline the importance of investigating NP in both sexes.

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What makes surgical nerve injury painful? A 4-year to 9-year follow-up of patients with intercostobrachial nerve resection in women treated for breast cancer

Abstract: Supplemental Digital Content is Available in the Text.Longitudinal study of 251 patients with surgical intercostobrachial nerve resection. Other chronic pains, psychological burden, inflammatory markers, and central sensitization characterize chronic postsurgical neuropathic pain.

Cited by 47 publications

References 46 publications

Machine-learned identification of psychological subgroups with relation to pain interference in patients after breast cancer treatments

Machine-learned identification of psychological subgroups with relation to pain interference in patients after breast cancer treatments

Capturing Novel Non-opioid Pain Targets

Spared nerve injury causes sexually dimorphic mechanical allodynia and differential gene expression in spinal cords and dorsal root ganglia in rats

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