Long-term intrathecal administration of morphine vs. baclofen: Differences in CSF glycoconjugate profiles using multiglycomics.

Opioid use for treatment of persistent pain has increased dramatically over the past two decades, but it has not resulted in improved pain management outcomes. To understand the molecular mechanisms of opioids, molecular signatures that arise from opioid exposure are often sought after, using various analytical methods. In this study, we performed proteomics, and multiglycomics via sequential analysis of polysialic acids, glycosaminoglycans, N-glycans and O-glycans, using the same cerebral spinal fluid (CSF) sample from patients that had long-term (>2 years), intrathecal morphine or baclofen administered via an indwelling pump. Proteomics and N-glycomics signatures between the two treatment groups were highly conserved, while significant differences were observed in polysialic acid, heparan sulfate glycosaminoglycan and O-glycan profiles between the two treatment groups. This represents the first study to investigate the potential relationships between diverse CSF conjugated glycans and long-term intrathecal drug exposure. The unique changes, observed by a sequential analytical workflow, reflect previously undescribed molecular effects of opioid administration and pain management.

Sleep disordered breathing and chronic respiratory failure in patients with chronic pain on long term opioid therapy.

STUDY OBJECTIVES: The use of opioid medication for chronic pain has been increasing. The main aim of this study was to assess how many patients on opioids for chronic pain had sleep disordered breathing (SDB) and the type of SDB. The impact of these medications on daytime arterial blood gas (ABG) measurements and psychomotor vigilance was also studied. METHODS: Twenty-four patients (aged 18-75 years) on long-term opioids were prospectively recruited. Patients underwent home polysomnogram (PSG), psychomotor vigilance testing (PVT), and awake daytime ABG. Overnight PSG findings were compared to those of patients matched for age, sex, and BMI referred to our sleep service for evaluation of SDB. PVT results in the patient cohort were compared to PVT in healthy controls. RESULTS: Forty-six percent of opioid patients had severe SDB as defined by an apnea hypopnea index (AHI) > 30/h. The severity of SDB was similar in opioid-treated pain clinic patients and sleep clinic patients (mean ± SD AHI: Opioid-treated patients 32.7 ± 25.6; Sleep Study comparator group 28.9 ± 24.6, p = 0.6). Opioid patients had a higher frequency of central apneas and a lower arousal index (CAI: 3.9 ± 8.3 vs. 0.3 ± 0.5 events/h; p = 0.004, AI 8.0 ± 4.1 vs. 20.1 ± 13.8, p < 0.001). Pain clinic patients had impaired gas exchange during sleep and wakefulness. Nine of 20 (45%) had daytime hypercapnia, indicating a surprising number were in chronic respiratory failure. Morphine equivalent doses correlated with the severity of SDB. PVT was impaired when compared to a healthy PVT comparator group (RT: Opioid-treated patients 0.43 ± 0.27: Healthy PVT comparator group 0.28 ± 0.03 sec; p < 0.001). CONCLUSIONS: Patients on long-term opioids frequently have severe SDB, which in part is central in origin. PVT was markedly impaired. Half of the patients studied have evidence of chronic ventilatory failure. COMMENTARY: A commentary on this article appears in this issue on page 853

Validation of the Chronic Pain Acceptance Questionnaire-8 in an Australian pain clinic sample.

BACKGROUND: Recently, an 8-item short-form version of the Chronic Pain Acceptance Questionnaire (CPAQ-8) was developed predominantly in an internet sample. Further investigation of the factor structure in a multidisciplinary pain clinic sample is required. Investigation of the concurrent validity of the CPAQ-8 after accounting for the effects of variables commonly measured in the pain clinic setting is also necessary. PURPOSE: This study examines the factor structure and concurrent validity of the CPAQ-8 in a sample of treatment-seeking patients who attended a multidisciplinary pain clinic. METHODS: Participants were 334 patients who attended an Australian multidisciplinary pain service. Participants completed the CPAQ, a demographic questionnaire, and measures of patient adjustment and functioning. RESULTS: Confirmatory factor analysis identified a two-factor 8-item model consisting of Activity Engagement and Pain Willingness factors (SRMR = 0.039, RMSEA = 0.063, CFI = 0.973, TLI = 0.960) was superior to both the CPAQ and CPAQ with an item removed. The CPAQ and CPAQ-8 total scores were highly correlated (r = 0.93). After accounting for pain intensity, the CPAQ-8 was a significant predictor of depression, anxiety, stress, and disability. The subscales of the CPAQ-8 were both unique contributors to depression and disability in regression analyses, after accounting for pain intensity and kinesiophobia, and after accounting for pain intensity and catastrophizing. CONCLUSIONS: The CPAQ-8 has a sound factor structure and similar psychometric properties to the CPAQ; it may have clinical utility as a measure of pain acceptance in treatment-seeking, chronic pain patients.

Six month post-treatment deterioration in acceptance (CPAQ-8) and cognitions following multidisciplinary pain treatment.

Pain acceptance contributes significantly to the effectiveness of pain treatment outcomes. Nevertheless, little research has been conducted to examine whether a decrease in acceptance contributes to a deterioration in post treatment functioning. The aim of this study was to assess the role of pain acceptance in relation to process and outcome variables in the six-months following the conclusion of a pain program. Adults with chronic pain (N = 120) completed assessments at the completion of a 3-week multidisciplinary treatment program and 6-months post-treatment. Process measures included the Chronic Pain Acceptance Questionnaire-8 (CPAQ-8); the catastrophizing scale of the Pain Response Self-Statement Scale; the coping cognitions scale of the Pain Response Self-Statement Scale; and the Tampa Scale of Kinesiophobia. Outcome measures included the Roland Morris Disability Questionnaire; the depression scale of the Depression Anxiety and Stress Scale; and two measures of physical functioning. Deterioration in acceptance of pain was significantly associated with deterioration in depression and disability, even when catastrophizing cognitions and kinesiophobia were accounted for. Decrease in acceptance was the strongest predictor of reliable deterioration in depression and disability. Results indicated the CPAQ-8 has utility as a measure for monitoring patient functioning post-treatment.

Management of occupation-related musculoskeletal disorders.

Occupation-related musculoskeletal disorders are a common clinical problem. Management presents challenges in understanding the factors that give rise to work loss and disability. To improve outcomes, practitioners need to screen for risk factors, understand the demands of work and workplaces and be prepared to actively assist the process of work return. There are limitations with regard to many therapeutic modalities commonly used, though there are many useful adjuncts for the physician in achieving improved outcomes.

Neuropathic pain and diabetes.

Neuropathic pain is a common phenomenon resulting from injury to the central or peripheral nervous system. The means by which diabetes results in nerve injury is unclear but the effect is to cause injury at all levels of the nervous system from the level of the peripheral nerves to the brain. Nerve injury causes pain through a cascade of mechanisms resulting in altered processing of sensory input into the nervous system. This alteration occurs through chemical and anatomical changes in the nervous system that are similar to some of the processes seen in central sensitisation following acute pain. Following nerve injury, neuropathic pain occurs not only when these mechanisms are activated but also when sensitisation is maintained. Other processes occurring in neuropathic pain appear to be a loss of normal inhibitory controls as seen by a reduction in local GABA-ergic and descending monoaminergic influences. There are also important changes mediated via glial cells that can maintain neuropathic pain. Diabetes affects all areas of the nervous system and the contribution of higher levels of the nervous system is often overlooked. Neurophysiological and MRI evidence strongly suggest that these may contribute to the pain of diabetic neuropathy. Psychological dysfunction in diabetic patients is an important factor in increasing the suffering associated with all aspects of the disease, but treatment and control of pain can greatly improve the quality of life.