Pain in chemotherapy-induced neuropathy – More than neuropathic?

Abstract

Chemotherapy-induced neuropathy (CIN) is an adverse effect of chemotherapy. Pain in CIN might comprise neuropathic and nonneuropathic (ie, musculoskeletal) pain components, which might be characterized by pain patterns, electrophysiology, and somatosensory profiling. Included were 146 patients (100 female, 46 male; aged 56 ± 0.8 years) with CIN arising from different chemotherapy regimens. Patients were characterized clinically through nerve conduction studies (NCS) and quantitative sensory testing (QST). Questionnaires for pain (McGill) and anxiety/depression (Hospital Anxiety and Depression Scale) were supplied. Patients were followed-up after 17 days. Large- (61%) and mixed- (35%) fibre neuropathies were more frequent than small-fibre neuropathy (1.4%). The 5 major chemotherapeutic regimens impacted differently on large- but not on small-fibre function and did not predict painfulness. Chronic pain associated with CIN was reported in 41.7%. Painless and painful CIN did not differ in QST profiles or electrophysiological findings, but different somatosensory patterns were found in CIN subgroups (pain at rest [RestP], n = 25; movement-associated pain [MovP], n = 15; both pain characteristics [MovP+RestP], n = 21; or no pain [NonP], n = 85): small-fibre function (cold-detection threshold, CDT: z score: -1.46 ± 0.21, P < 0.01) was most impaired in RestP; mechanical hyperalgesia was exclusively found in MovP (z score: +0.81 ± 0.30, P < 0.05). "Anxiety" discriminated between painful and painless CIN; "CDT" and "anxiety" discriminated between patients with ongoing (RestP) and movement-associated pain (MovP) or pain components (MovP+RestP). The detrimental effect of chemotherapy on large fibres failed to differentiate painful from painless CIN. Patients stratified for musculoskeletal or neuropathic pain, however, differed in psychological and somatosensory parameters. This stratification might allow for the application of a more specific therapy.

Chemotherapy-induced pain and neuropathy

“…Owing to low estrogen levels and possible other unknown underlying mechanisms, adjuvant endocrine therapy is known to cause arthralgia, myalgia, joint stiffness, paresthesia, and carpal tunnel syndrome, 17 which may be misinterpreted as chemotherapy-induced neuropathic pain by both clinicians and patients. Recent studies have suggested that muscle and joint pain should be considered a part of the neuropathic syndrome, 9,11 but it is possible that these neuropathic-like symptoms are caused by endocrine therapy and are not a part of the CIPN syndrome. This is supported by results of a study on persistent sensory disturbances after adjuvant chemotherapy for breast cancer that showed that the endocrine treatment was a risk factor for peripheral sensory disturbances in the feet of patients receiving cyclophosphamide, epirubicin, and fluorouracil, which is not known to cause neuropathy and neuropathic pain.…”

“…26,29 Several studies have explored the incidence, predictors, and impact of CIPN, but less is known about CIPN-related pain. 21,24 Most studies have pooled patients with different types of cancer treated with different neurotoxic agents, 1,11 which complicates the interpretation of the results, because the incidence and type of CIPN are dependent on the specific chemotherapeutic agent used. 15 Additional therapies, such as surgery, radiation therapy, and endocrine therapy, can cause other types of neuropathy and pain 17 and are used to varying degrees, but this has rarely been discussed.…”

The Content Validity of a Chemotherapy-Induced Peripheral Neuropathy Patient-Reported Outcome Measure

“…Patients may also have difficulty typing, playing an instrument, using eating utensils, or picking up small objects, such as coins; such losses of independence and function can affect quality of life in the physical and psychological domains. Severe symptoms, particularly painful CIPN, are associated with sleep disturbance and psychological comorbidity (Desaulniers, 2011; Geber et al, 2013; Kautio et al, 2011; Mols et al, 2013; Smith et al, 2013; Tofthagen et al, 2013). Weakness, sensory ataxia, and diminished sensation may cause greater susceptibility to tripping, falls, ulcers, and burns, particularly in patients with diabetes (Tofthagen et al, 2012; Visovsky, Meyer, Roller, & Poppas, 2008).…”

State of the Science

“…In turn, this negatively impacts healthcare providers' ability to assess and manage TIMP effectively in clinical practice. These assertions are supported by a recent exploratory study 34 evaluating symptom patterns indicative of neuropathic or musculoskeletal pain, or both, in cancer patients; 1 major finding was that, although chemotherapy-induced neuropathyassociated pain is usually regarded as neuropathic, movementassociated pain in approximately 60% of patients points to a musculoskeletal pain component as evidenced by a subgroup of patients with different clinical, somatosensory, and psychological parameters. Furthermore, 1 characteristic of musculoskeletal pain is its association with weight bearing or physical exercise, which is different from persisting pain occurring at rest or at night that alleviates while walking and is characteristic of neuropathic pain.…”

“…Furthermore, 1 characteristic of musculoskeletal pain is its association with weight bearing or physical exercise, which is different from persisting pain occurring at rest or at night that alleviates while walking and is characteristic of neuropathic pain. 34 Interestingly, anxiety was higher in patients with musculoskeletal pain components that could be explained by anxiety as a known risk factor for musculoskeletal pain where activation of the sympathetic nervous system releases stress hormones leading to impairment of muscle functioning essential for control of movements and posture. 34,35 Therefore, one can infer that true estimates of prevalence cannot be determined without conceptual clarity of TIMP and the recognition of TIMP as separate and distinct from other types of treatmentrelated pain, as has been suggested by recent literature.…”