Meyke Roosink

Somatosensory Symptoms and Signs and Conditioned Pain Modulation in Chronic Post-Stroke Shoulder Pain

UNLABELLED Persistent shoulder pain is a common complication after stroke. Its etiology and underlying mechanisms are not well understood and treatment is generally unsatisfactory. The objective of this study was to assess the role of central sensitization and disinhibition in chronic stroke patients with chronic PSSP (n = 19), pain-free stroke patients (n = 29), and healthy controls (n = 23). Positive and negative somatosensory symptoms and signs were assessed using clinical examination and electrical and mechanical quantitative sensory testing (QST). Conditioned pain modulation (CPM) was assessed by comparing QST thresholds before and after applying a cold pressor test. Sensory abnormalities were more frequently observed and more severe in patients with PSSP, including positive signs such as allodynia at the affected side and generalized hyperalgesia at the unaffected side. CPM was similar in stroke patients and healthy controls. This study showed that chronic PSSP was associated with several positive and negative somatosensory signs, implicating a role for central sensitization and possibly for disinhibition. Since the causal relationship remains unclear, and may be related to either neuroplasticity induced by ongoing nociception as well as to the neuropathic brain lesion, prospective studies are warranted. PERSPECTIVE The assessment of somatosensory symptoms and signs and endogenous pain modulation demonstrated a role for central sensitization and possibly for disinhibition in chronic PSSP. Prevention and treatment of PSSP could benefit from a more detailed analysis of both peripheral and central pain mechanisms.

Persistent Shoulder Pain in the First 6 Months After Stroke: Results of a Prospective Cohort Study

OBJECTIVE To identify factors associated with persistent poststroke shoulder pain (pPSSP) in the first 6 months after stroke. DESIGN Prospective inception cohort study. SETTING Stroke units of 2 teaching hospitals. PARTICIPANTS Patients (N=31) with a clinical diagnosis of stroke. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES The development of pPSSP within the first 6 months after stroke. Clinical assessment of motor, somatosensory, cognitive, emotional, and autonomic functions, undertaken within 2 weeks (t0), at 3 months (t1), and at 6 months (t2) after stroke. RESULTS Patients with pPSSP (n=9) were compared with patients without pPSSP (n=22). Bivariate logistic regression analyses showed that pPSSP was significantly associated with impaired voluntary motor control (t0, t1, t2), diminished proprioception (t0, t1), tactile extinction (t0), abnormal sensation (t1, t2), spasticity of the elbow flexor muscles (t1, t2), restricted range of motion (ROM) for both shoulder abduction (t2) and shoulder external rotation (t1, t2), trophic changes (t1), and type 2 diabetes mellitus (t0). CONCLUSIONS These findings suggest a multifactorial etiology of pPSSP. The association of pPSSP with restricted, passive, pain-free ROM and signs indicative of somatosensory sensitization may implicate a vicious cycle of repetitive (micro)trauma that can establish itself rapidly after stroke. Intervention should therefore be focused on maintaining and restoring joint ROM as well as preventing injury and somatosensory sensitization. In this perspective, strategies that aim to intervene simultaneously at various levels of function can be expected to be more effective than treatment directed at merely 1 level.

Altered cortical somatosensory processing in chronic stroke: A relationship with post-stroke shoulder pain

Post-stroke shoulder pain (PSSP), traditionally regarded as purely nociceptive pain, is often persistent and the mechanisms underlying the pain complaints are not well understood. This explorative study is the first to address the possible changes in cortical somatosensory processing in patients with PSSP. Cortical potentials were recorded following intracutaneous electrostimulaton in stroke patients with chronic PSSP (n= 6), pain-free stroke patients (PF, n=14) and healthy controls (HC, n=20) using EEG. Amplitudes and latencies of both sensory discriminative (N90) as well as cognitive evaluative (N150, P200, the N150-P200 peak-to-peak difference and P300) evoked potential components were evaluated. Stroke was associated with reduced N150 and P300 amplitudes and increased N90, N150 and P300 latencies at both sides. Compared to PF and HC, the P200 and N150-P200 latencies were increased in PSSP patients after stimulation at both sides, even when comparing subgroups with similar lesion size and location. Stroke was associated with reduced sensory-discriminative as well as with reduced cognitive-evaluative cortical somatosensory processing. This reduction was more pronounced in patients with PSSP and may be related to the central effects of persistent nociceptive pain.

Towards a mechanism-based view on post-stroke shoulder pain: Theoretical considerations and clinical implications

The assessment and treatment of post-stroke shoulder pain (PSSP) is largely based on the assumption that pain is due to biomechanical alterations within the shoulder joint after stroke. However, current treatment often provides limited pain relief, leading to a considerable number of patients with persistent pain. This suggests that PSSP may not be merely due to simple nociception from the shoulder joint. A better understanding of the neurophysiological mechanisms underlying the development and perpetuation of PSSP is needed. Here, a theoretical framework for presumed PSSP mechanisms and their assessment is presented based on key concepts applied in pain research. This theoretical framework assumes that although pain may be localized in one region of the body, the mechanisms causing pain may occur at any level of the somatosensory neuro-axis. Detailed assessment of pain complaints and somatosensory abnormalities should, therefore, be a key element in clinical PSSP research. Studies aiming to further characterize somatosensory functions in patients with PSSP (initially) need to take a broad methodological approach including both clinical as well as more experimental pain research tools, such as quantitative sensory testing. A better understanding of pain mechanisms may explain why persistent PSSP and unsatisfactory pain relief are common despite active prevention and treatment strategies and may provide a basis for improved clinical management of PSSP.

Defining post-stroke pain: diagnostic challenges.

Recently, a new grading system for central post-stroke pain (CPSP) was proposed, which might be used to distinguish patients with stroke who have central neuropathic pain from patients who have peripheral pain. Accordingly, for a CPSP diagnosis, all other causes of pain have to be excluded. Although this criterion has its purpose for defining CPSP as a separate entity, a too rigorous distinction between central and peripheral post-stroke pain might have drawbacks as well. Most importantly, by strictly following the proposed grading system, central pain mechanisms could be missed or even disputed in patients with other types of post-stroke pain. This possibility is particularly relevant as “mixed” pain and pre-existing pain are common after stroke.1 For this reason, we would like to emphasize that peripheral nociceptive pain after stroke might coincide with symptoms characteristic of CPSP. To lend support to our concern, we present recent data on post-stroke shoulder pain (PSSP).

Classifying post-stroke shoulder pain: Can the DN4 be helpful?

The etiology of post‐stroke shoulder pain (PSSP) is largely unclear and may involve both nociceptive and neuropathic mechanisms. No gold standard is present for PSSP diagnosis. The neuropathic pain diagnostic questionnaire (DN4), was originally developed to identify neuropathic pain in the clinical context. In this study we used the DN4 to categorize PSSP patients and compared symptoms and signs suggestive of either nociceptive or neuropathic pain. Pain complaints and sensory functions were compared between patients with chronic PSSP scoring at least four (DN4+, n=9) or less than four (DN4−, n=10) on the DN4. Pain was assessed using a numeric rating scale and the McGill pain questionnaire. Sensory functions were assessed using clinical examination and quantitative sensory testing combined with a cold pressor test. Patients classified as DN4+ reported constant pain, higher pain intensity, a higher impact of pain on daily living, more frequent loss of cold sensation, reduced QST thresholds at the unaffected side and increased QST thresholds at the affected side. Notably, several symptoms and signs suggestive of either neuropathic or nociceptive pain corresponded to the subgroups DN4+ and DN4− respectively. However, since the pathophysiological mechanisms remain unclear and none of the sensory signs could be exclusively related to either DN4+ or DN4−, PSSP prognosis and treatment should not be solely based on the DN4. Nonetheless, a thorough assessment of neuropathic and nociceptive pain complaints and somatosensory functions should be included in the diagnostic work‐up of PSSP.

RE: Underlying pathology and associated factors of hemiplegic shoulder pain.

Poststroke shoulder pain or hemiplegic shoulder pain (HSP) is a complex type of pain that has been the topic of many literature reviews. Traditionally, HSP is viewed as a nociceptive pain. Nonetheless, both the clinical features and the underlying mechanisms may show similarities to other types of poststroke pain, such as shoulder-hand syndrome (i.e., complex regional pain syndrome type 1) and central poststroke pain. As such, central pain mechanisms may play an important role in the development and in the perpetuation of HSP.1 In a recent literature review on the underlying pathology and associated factors of HSP, a theoretical framework was proposed, illustrating how altered peripheral and central nervous activity may contribute to the development of (persistent) HSP.2 According to the authors, however, convincing data on somatosensory sensitization were lacking at the time of the literature search (until September 2010). However, recently published data from our clinical research program indeed indicate an important role for somatosensory sensitization in HSP.3–5

Central neuropathic mechanisms in post-stroke shoulder pain

Central neuropathic pain mechanisms may play a larger role in chronic PSSP than is traditionally assumed. With the DN4, it is possible to select a subgroup of PSSP patients with more severe pain complaints and sensory abnormalities. Subgroup identification based on the DN4 might be used in future longitudinal and intervention studies to further explore the mechanisms underlying PSSP.

Persistent shoulder pain after stroke

Shoulder pain is a common complication after stroke, but its etiology is poorly understood. Treatment is generally unsatisfactory and chronic pain is common. This thesis adopts a mechanism-based approach to the research of PSSP development. The primary objective of the thesis is to obtain a better understanding of the pathophysiological mechanisms responsible for the development of persistent PSSP (pPSSP). Chapter 2 introduces the terminology and the neurophysiological concepts of pain and describes the theoretical framework that is used in the subsequent chapters. Subsequently, 3 cross-sectional studies are described that assessed chronic stroke patients with pPSSP by using pain research tools such as quantitative sensory testing and conditioned pain modulation (Chapter 3), cortical evoked potentials (Chapter 4), and the neuropathic pain diagnostic questionnaire (Chapter 5). The last part of the thesis focuses on the longitudinal assessment of pPSSP within 2 weeks, at 3 months and at 6 months after stroke. Chapter 6 describes the assessment of the complete clinical picture of somatosensory, motor, cognitive, emotional and autonomic functions in patient developing pPSSP. In chapter 7 the relationship between pPSSP and somatosensory loss, somatosensory sensitization and endogenous pain inhibition is studied. In summary, pPSSP was associated with both somatosensory loss and somatosensory sensitization as well as with altered central somatosensory processing. Moreover, in the chronic phase after stroke many patients with pPSSP reported neuropathic-like pain complaints. The influence of the presumed initiating factors may gradually decrease during the persistence of PSSP. Pain perpetuation may be related to a vicious circle of pain, limited range of motion, re-injury and somatosensory sensitization which may establish quite rapidly (i.e. within 3 months after PSSP onset) and may persist into the chronic phase after stroke. These studies confirm the multi-factorial etiology of pPSSP. Ongoing nociception, the brain lesion itself, and other (premorbid) factors may contribute to the development of pPSSP. Although the precise neurophysiological mechanisms still remain unclear, these findings have important implications for the assessment, prevention and treatment of PSSP.