Sensory profiles in women with neuropathic pain after breast cancer surgery

L Mustonen, J Vollert, A S C Rice, E Kalso, H Harno, L Mustonen, J Vollert, A S C Rice, E Kalso, H Harno

Abstract

Purpose: We performed a detailed analysis of sensory function in patients with chronic post-surgical neuropathic pain (NP) after breast cancer treatments by quantitative sensory testing (QST) with DFNS (German Research Network on Neuropathic Pain) protocol and bed side examination (BE). The nature of sensory changes in peripheral NP may reflect distinct pathophysiological backgrounds that can guide the treatment choices. NP with sensory gain (i.e., hyperesthesia, hyperalgesia, allodynia) has been shown to respond to Na+-channel blockers (e.g., oxcarbazepine).

Methods: 104 patients with at least "probable" NP in the surgical area were included. All patients had been treated for breast cancer 4-9 years ago and the handling of the intercostobrachial nerve (ICBN) was verified by the surgeon. QST was conducted at the site of NP in the surgical or nearby area and the corresponding contralateral area. BE covered the upper body and sensory abnormalities were marked on body maps and digitalized for area calculation. The outcomes of BE and QST were compared to assess the value of QST in the sensory examination of this patient group.

Results: Loss of function in both small and large fibers was a prominent feature in QST in the area of post-surgical NP. QST profiles did not differ between spared and resected ICBN. In BE, hypoesthesia on multiple modalities was highly prevalent. The presence of sensory gain in BE was associated with more intense pain.

Conclusions: Extensive sensory loss is characteristic for chronic post-surgical NP several years after treatment for breast cancer. These patients are unlikely to respond to Na+-channel blockers.

Keywords: Neuropathic pain; Post-surgical pain; Quantitative sensory testing; Sensory mapping.

Conflict of interest statement

JV has received consulting fees from CASQUAR, outside of this work. EK reports advisory board memberships in Orion Pharma, Grünenthal and Pierre Fabre, outside of this work. Other authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Patient flow chart
Fig. 2
Fig. 2
Comparison of the QST profiles on affected (surgical) and unaffected side. QST was performed on the area of breast in 43 (41%) and on the area of ICBN innervation (lateral breast, upper side of chest, axilla, upper medial arm) in 61 (59%). CDT cold detection threshold, CPT cold pain threshold, DMA dynamic mechanical allodynia, HPT heat pain threshold, ICBN intercostobrachial nerve, MDT mechanical detection threshold, MPS mechanical pain sensitivity, MPT mechanical pain threshold, NRS numerical rating scale, PHS paradoxal heat sensation, PPT pressure pain threshold, QST quantitative sensory testing, VDT vibration detection threshold, WDT warm detection threshold, WUR wind-up ratio
Fig. 3
Fig. 3
QST profiles for patients with spared (n = 11), partially (n = 26), and totally (n = 20) resected ICBN. CDT cold detection threshold, CPT cold pain threshold, DMA dynamic mechanical allodynia, HPT heat pain threshold, ICBN intercostobrachial nerve, MDT mechanical detection threshold, MPS mechanical pain sensitivity, MPT mechanical pain threshold, NRS numerical rating scale, PHS paradoxal heat sensation, PPT pressure pain threshold, QST quantitative sensory testing, VDT vibration detection threshold, WDT warm detection threshold, WUR wind-up ratio
Fig. 4
Fig. 4
Sensory phenotypes for breast conserving resection (BCR) and mastectomy
Fig. 5
Fig. 5
Areas of sensory abnormalities in BE on the side of surgery in patients with SLNB or ALND. Overlap of areas of sensory loss or gain in BE including light touch (cotton tuft), dynamic touch (painter’s brush), static allodynia (compression of finger), pinprick (cocktail stick), cold and warm sensation (metal roller). Sensory loss refers to hypoestesia and sensory gain refers to hyperestesia, dysestesia, or allodynia in any of these sensory modalities. For clarity, all surgeries are shown on left side. ALND axillary lymph node dissection, BE bedside examination, ICBN intercostobrachial nerve, SLNB sentinel lymph node biopsy

References

    1. Haroutiunian S, Nikolajsen L, Finnerup NB, et al. The neuropathic component in persistent postsurgical pain: a systematic literature review. Pain. 2013;154:95–102. doi: 10.1016/j.pain.2012.09.010.
    1. Ilhan E, Chee E, Hush J, et al. The prevalence of neuropathic pain is high after treatment for breast cancer: a systematic review. Pain. 2017;158:2082–2091. doi: 10.1097/j.pain.0000000000001004.
    1. Mejdahl MK, Andersen KG, Gartner R, et al. Persistent pain and sensory disturbances after treatment for breast cancer: six year nationwide follow-up study. BMJ. 2013;346:f1865. doi: 10.1136/bmj.f1865.
    1. Mustonen L, Aho T, Harno H, et al. 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. Pain. 2019;160:246–256. doi: 10.1097/j.pain.0000000000001398.
    1. Pereira S, Fontes F, Sonin T, et al. Neuropathic pain after breast cancer treatment: characterization and risk factors. J Pain Symptom Manag. 2017;54:877. doi: 10.1016/j.jpainsymman.2017.04.011.
    1. Warrier S, Hwang S, Koh CE, et al. Preservation or division of the intercostobrachial nerve in axillary dissection for breast cancer: meta-analysis of randomised controlled trials. Breast. 2014;23:310–316. doi: 10.1016/j.breast.2014.01.014.
    1. Jung BF, Ahrendt GM, Oaklander AL, et al. Neuropathic pain following breast cancer surgery: proposed classification and research update. Pain. 2003;104:1–13. doi: 10.1016/S0304-3959(03)00241-0.
    1. Baron R, Binder A, Wasner G. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol. 2010;9:807–819. doi: 10.1016/S1474-4422(10)70143-5.
    1. Maier C, Baron R, Tolle TR, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes. Pain. 2010;150:439–450. doi: 10.1016/j.pain.2010.05.002.
    1. Demant DT, Lund K, Vollert J, et al. The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: a randomised, double-blind, placebo-controlled phenotype-stratified study. Pain. 2014;155:2263–2273. doi: 10.1016/j.pain.2014.08.014.
    1. Treede RD. The role of quantitative sensory testing in the prediction of chronic pain. Pain. 2019;160(Suppl 1):S66–S69. doi: 10.1097/j.pain.0000000000001544.
    1. Cruccu G, Sommer C, Anand P, et al. EFNS guidelines on neuropathic pain assessment: revised 2009. Eur J Neurol. 2010;17:1010–1018. doi: 10.1111/j.1468-1331.2010.02969.x.
    1. Baron R, Maier C, Attal N, et al. Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles. Pain. 2017;158:261–272. doi: 10.1097/j.pain.0000000000000753.
    1. Vollert J, Maier C, Attal N, et al. Stratifying patients with peripheral neuropathic pain based on sensory profiles: algorithm and sample size recommendations. Pain. 2017;158:1446–1455. doi: 10.1097/j.pain.0000000000000935.
    1. Andersen KG, Duriaud HM, Kehlet H, et al. The relationship between sensory loss and persistent pain 1 year after breast cancer surgery. J Pain. 2017;18:1129–1138. doi: 10.1016/j.jpain.2017.05.002.
    1. Gottrup H, Andersen J, Arendt-Nielsen L, et al. Psychophysical examination in patients with post-mastectomy pain. Pain. 2000;87:275–284. doi: 10.1016/S0304-3959(00)00291-8.
    1. Schreiber KL, Martel MO, Shnol H, et al. Persistent pain in postmastectomy patients: comparison of psychophysical, medical, surgical, and psychosocial characteristics between patients with and without pain. Pain. 2013;154:660–668. doi: 10.1016/j.pain.2012.11.015.
    1. Demant DT, Lund K, Finnerup NB, et al. Pain relief with lidocaine 5% patch in localized peripheral neuropathic pain in relation to pain phenotype: a randomised, double-blind, and placebo-controlled, phenotype panel study. Pain. 2015;156:2234–2244. doi: 10.1097/j.pain.0000000000000266.
    1. Vollert J, Attal N, Baron R, et al. Quantitative sensory testing using DFNS protocol in Europe: an evaluation of heterogeneity across multiple centers in patients with peripheral neuropathic pain and healthy subjects. Pain. 2016;157:750–758. doi: 10.1097/j.pain.0000000000000433.
    1. Meyer-Frießem CH, Attal N, Baron R, et al. Pain thresholds and intensities of CRPS type I and neuropathic pain in respect to sex. Eur J Pain. 2020 doi: 10.1002/ejp.1550.
    1. Dezawa K, Noma N, Watanabe K, et al. Short-term effects of orthognathic surgery on somatosensory function and recovery pattern in the early postoperative period. J Oral Sci. 2016;58:177–184. doi: 10.2334/josnusd.15-0670.
    1. Kaunisto MA, Jokela R, Tallgren M, et al. Pain in 1,000 women treated for breast cancer: a prospective study of pain sensitivity and postoperative pain. Anesthesiology. 2013;119:1410–1421. doi: 10.1097/ALN.0000000000000012.
    1. Finnerup NB, Haroutounian S, Kamerman P, et al. Neuropathic pain: an updated grading system for research and clinical practice. Pain. 2016;157:1599–1606. doi: 10.1097/j.pain.0000000000000492.
    1. Andersen KG, Aasvang EK, Kroman N, et al. Intercostobrachial nerve handling and pain after axillary lymph node dissection for breast cancer. Acta Anaesthesiol Scand. 2014;58:1240–1248. doi: 10.1111/aas.12393.
    1. Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singapore. 1994;23:129–138.
    1. Rolke R, Baron R, Maier C, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain. 2006;123:231–243. doi: 10.1016/j.pain.2006.01.041.
    1. Pfau DB, Krumova EK, Treede RD, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): reference data for the trunk and application in patients with chronic postherpetic neuralgia. Pain. 2014;155:1002–1015. doi: 10.1016/j.pain.2014.02.004.
    1. Vollert J, Magerl W, Baron R, et al. Pathophysiological mechanisms of neuropathic pain: comparison of sensory phenotypes in patients and human surrogate pain models. Pain. 2018;159:1090–1102. doi: 10.1097/j.pain.0000000000001190.
    1. Vilholm OJ, Cold S, Rasmussen L, et al. Sensory function and pain in a population of patients treated for breast cancer. Acta Anaesthesiol Scand. 2009;53:800–806. doi: 10.1111/j.1399-6576.2009.01938.x.
    1. Schuning J, Scherens A, Haussleiter IS, et al. Sensory changes and loss of intraepidermal nerve fibers in painful unilateral nerve injury. Clin J Pain. 2009;25:683–690. doi: 10.1097/AJP.0b013e3181a1260e.
    1. Fernandez-Lao C, Cantarero-Villanueva I, Fernandez-de-las-Penas C, et al. Widespread mechanical pain hypersensitivity as a sign of central sensitization after breast cancer surgery: comparison between mastectomy and lumpectomy. Pain Med. 2011;12:72–78. doi: 10.1111/j.1526-4637.2010.01027.x.
    1. Andersen KG, Duriaud HM, Jensen HE, et al. Predictive factors for the development of persistent pain after breast cancer surgery. Pain. 2015;156:2413–2422. doi: 10.1097/j.pain.0000000000000298.
    1. Simpson DM, Schifitto G, Clifford DB, et al. Pregabalin for painful HIV neuropathy: a randomized, double-blind, placebo-controlled trial. Neurology. 2010;74:413–420. doi: 10.1212/WNL.0b013e3181ccc6ef.
    1. Campbell JN, Meyer RA. Mechanisms of neuropathic pain. Neuron. 2006;52:77–92. doi: 10.1016/j.neuron.2006.09.021.
    1. La Cesa S, Sammartino P, Mollica C, et al. A longitudinal study of painless and painful intercostobrachial neuropathy after breast cancer surgery. Neurol Sci. 2018;39:1245–1251. doi: 10.1007/s10072-018-3418-y.
    1. Jensen TS, Finnerup NB. Allodynia and hyperalgesia in neuropathic pain: clinical manifestations and mechanisms. Lancet Neurol. 2014;13:924–935. doi: 10.1016/S1474-4422(14)70102-4.
    1. Leffler AS, Hansson P. Painful traumatic peripheral partial nerve injury-sensory dysfunction profiles comparing outcomes of bedside examination and quantitative sensory testing. Eur J Pain. 2008;12:397–402. doi: 10.1016/j.ejpain.2007.08.009.
    1. Teerijoki-Oksa T, Forssell H, Jaaskelainen SK. Validation of diagnostic methods for traumatic sensory neuropathy and neuropathic pain. Muscle Nerve. 2019;59:342–347. doi: 10.1002/mus.26400.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj