Expectations of treatment outcome in complex cases of patients with chronic pain: A study on the DATAPAIN cohort.

BACKGROUND: A better insight in how the biopsychosocial factors influence patient outcome(s) may provide information that helps selecting the optimal pain management for a specific group. METHODS: Categorization was made in the prospective DATAPAIN registry, in which patients with pain severity (Numeric Rating Scale [NRS]: 7-10), depression or anxiety (Hospital Anxiety and Depression Scale: > 10), and pain catastrophizing (Pain Catastrophizing Scale: > 31) were identified as complex cases. Patient outcomes; treatment satisfaction on the Patient Global Impression of Change (PGIC), pain relief (NRS), pain interference on the Brief Pain Inventory (BPI) and quality of life indicator General Perceived Health (GPH) were evaluated. Logistic regression analyzed if belonging to the complex cases showed modification in the outcome of the PGIC and GPH. Linear regression was observed if complex cases differed in average reduction in pain relief and interference compared to non-complex cases. RESULTS: 1637 patients were included, of which 345 (21.08%) were considered complex cases. The changes in scores of pain relief and BPI active subscale were not significantly different between groups. The BPI affective subscale had a different change in score (-0.509; p: 0.002). The complex cases had an odds ratio (OR) of 0.59 (95% confidence interval [CI]: 0.36-0.77) on treatment satisfaction compared to non-complex cases, and an OR of 0.28 (95% CI: 0.11-0.56) on the GPH. CONCLUSION: When treating patients with complex cases, desired treatment outcome(s) should be recognized by specialists and patients, as these may be less likely to occur.

Korsakoff syndrome and altered pain perception: a search of underlying neural mechanisms.

OBJECTIVES: Patients with Korsakoff syndrome (KS) may have a diminished pain perception. Information on KS and pain is scarce and limited to case descriptions. The present study is the first to investigate the underlying neural mechanisms of altered pain perception in patients with KS more systematically. METHODS: We conducted a literature search on neural correlates of pain perception in other neurocognitive disorders in which extensive research was done. RESULTS: The brain areas that are affected in KS showed considerable overlap with the neural correlates of pain perception in other neurocognitive disorders. We discussed which different aspects of disturbed pain perception could play a role within KS, based on distinct neural damage and brain areas involved in pain perception. CONCLUSIONS: Combining current knowledge, we hypothesize that diminished pain perception in KS may be related to lesioned neural connections between cerebral cortical networks and relays of mainly the thalamus, the periaqueductal gray, and possibly lower brain stem regions projecting to the cerebellum. Based on these neural correlates of altered pain perception, we assume that increased pain thresholds, inhibition of pain signals, and disturbed input to cerebral and cerebellar cortical areas involved in pain processing, all are candidate mechanisms in cases of diminished pain perception in KS. We recommend that clinicians need to be alert for somatic morbidity in patients with KS. Due to altered neural processing of nociceptive input the clinical symptoms of somatic morbidity may present differently (i.e. limited pain responses) and therefore are at risk of being missed.

The Pain Dynamics of Small Fiber Neuropathy.

Pain is a central feature in small fiber neuropathy (SFN), with only moderate effects of pharmacologic treatment. The evaluation of the efficacy of therapies on pain has been driven by static measures, and a circadian cycle has been suggested. The aim of this study is to evaluate the pain dynamics in SFN. A total of 165 patients completed a standardized pain diary 4 times per week over a 4-week period. Patients used the 11-point numeric rating scale for average diurnal, nocturnal, and maximum pain, taking into account the circumstances in which pain emerged most. Medication used, SFN-related complaints, sleep quality, and anatomic location of pain were also assessed. Neuropathic pain showed a length-dependent pattern. For pain intensity, marginal higher pain scores at night than during the day were shown, likely not clinically meaningful, with stable lower pain intensities in weekends compared with weekdays. The average pain intensity was stable during the 4-week period. Maximum pain was experienced mainly at rest and during sleep. Besides, pain intensity at night showed an inverse relationship with quality of sleep. In conclusion, for trials in SFN it is justified to use pain scores from any time of the day during short measurement periods. PERSPECTIVE: This article presents for the first time the pain dynamics of SFN. The effect of pharmacologic treatment in SFN is often disappointing, partly owing to insufficient trial designs. The results of this study have added value in the development of new proper clinical trials in SFN.

Painful Diabetic Neuropathy Anxiety Rasch-Transformed Questionnaire (PART-Q30(©) ).

The association between painful diabetic neuropathy (PDN) and anxiety has been acknowledged using various anxiety scales capturing various fear entities. It has never been examined whether these generally applied anxiety questionnaires could be pooled to construct one overall anxiety metric. After completion by a cohort of 151 patients with PDN, data obtained from seven generally applied fear scales were stacked (n = 88 items) and subjected to Rasch analyses (pre-PART-Q88) to create the PDN overall Anxiety Questionnaire (PART-Q30(©) ). We subsequently examined the impact of the final constructed PART-Q30(©) on disability and Quality of Life (QoL) using the Rasch-Transformed Pain Disability Index (RT-PDI) and the Norfolk Quality of Life Questionnaire, Diabetic Neuropathy version (RT-Norfolk). The pre-PART-Q88 data did not meet Rasch model's expectations. Through stepwise examination for model fit, disordered thresholds, local dependency and item bias, we succeeded in reducing the data and constructing a 30 items overall anxiety scale (PART-Q30(©) ) that fulfilled all model's expectations, including unidimensionality. An acceptable internal reliability was found (person-separation-index: 0.90). PART-Q30(©) explained 36% of disability and combined with RT-PDI 63% of QoL (assessed with RT-Norfolk).

Neuropathic Pain due to Small Fiber Neuropathy in Aging: Current Management and Future Prospects.

Over the last 10 years, the diagnosis small fiber neuropathy (SFN) has gained recognition worldwide. Patients often suffer from severe neuropathic pain that may be difficult to treat. A substantial subset of patients with SFN is aged 65 years or older, and these patients often exhibit comorbidities and usage of multiple drugs, making neuropathic pain treatment more challenging. In this review, we highlight relevant pathophysiological aspects and discuss currently used therapeutic strategies for neuropathic pain. Possible pitfalls in neuropathic pain treatment in the elderly will be underlined.

Improving assessment in small fiber neuropathy.

Interval measures at the impairment level addressing symptoms and at the activity/participation level addressing daily and social restrictions have not been developed for small fiber neuropathy (SFN). We developed an SFN-specific Rasch-built overall disability scale (SFN-RODS©), an activity/participation scale at the interval level. A preliminary SFN-RODS containing 146 activity/participation items was assessed twice (reliability studies) in 238 patients with SFN. The ordinal-based 13-item SFN-symptoms inventory questionnaire (SFN-SIQ©) and pain-visual-analogue-scale were also assessed (validity studies). The pre-SFN-RODS and SFN-SIQ data were subjected to the Rasch analyses. The pre-SFN-RODS did not meet Rasch model expectations. Based on requirements, such as misfit statistics, differential item functioning, and local dependency, items were systematically removed and model fit improved. Finally, a 32-item SFN-RODS© scale was constructed that fulfilled all Rasch requirements, demonstrating acceptable reliability and validity scores. The 13-item SFN-SIQ© was successfully transformed to an interval Rasch-built measure fulfilling model's requirements. In conclusion, the 32-item SFN-RODS© is a disease-specific interval measure suitable for detecting activity limitations and participation restrictions in patients with SFN. The 13-item SFN-SIQ© was transformed through Rasch to an interval measure. The use of these scales is recommended in future clinical interventional trials involving patients with SFN.

Painful neuropathies: the emerging role of sodium channelopathies.

Pain is a frequent debilitating feature reported in peripheral neuropathies with involvement of small nerve (Aδ and C) fibers. Voltage-gated sodium channels are responsible for the generation and conduction of action potentials in the peripheral nociceptive neuronal pathway where NaV 1.7, NaV 1.8, and NaV 1.9 sodium channels (encoded by SCN9A, SCN10A, and SCN11A) are preferentially expressed. The human genetic pain conditions inherited erythromelalgia and paroxysmal extreme pain disorder were the first to be linked to gain-of-function SCN9A mutations. Recent studies have expanded this spectrum with gain-of-function SCN9A mutations in patients with small fiber neuropathy and in a new syndrome of pain, dysautonomia, and small hands and small feet (acromesomelia). In addition, painful neuropathies have been recently linked to SCN10A mutations. Patch-clamp studies have shown that the effect of SCN9A mutations is dependent upon the cell-type background. The functional effects of a mutation in dorsal root ganglion (DRG) neurons and sympathetic neuron cells may differ per mutation, reflecting the pattern of expression of autonomic symptoms in patients with painful neuropathies who carry the mutation in question. Peripheral neuropathies may not always be length-dependent, as demonstrated in patients with initial facial and scalp pain symptoms with SCN9A mutations showing hyperexcitability in both trigeminal ganglion and DRG neurons. There is some evidence suggesting that gain-of-function SCN9A mutations can lead to degeneration of peripheral axons. This review will focus on the emerging role of sodium channelopathies in painful peripheral neuropathies, which could serve as a basis for novel therapeutic strategies.