Osteoarthritis pain has a significant neuropathic component: an exploratory in vivo patient model.

Osteoarthritis is the most common form of arthritis and includes manifestations of both nociceptive and neuropathic mechanisms. Intravenous lignocaine, a sodium channel blocker and neuronal membrane stabiliser, has been shown in controlled trials to be effective in neuropathic pain; however, the outcome of intravenous lignocaine in osteoarthritis patients has not been assessed yet. The existence of a neuropathic component to the pain of osteoarthritis was investigated by examining possible benefits upon sensory aspects of pain in osteoarthritis patients receiving intravenous lignocaine therapy. Retrospective observational study was carried out using health data routinely collected for non-research purposes. Patients with generalised osteoarthritis who had not responded to more conservative treatments were recruited sequentially and scheduled for intravenous lignocaine therapy either in the rheumatology or pain relief departments. Assessment of efficacy was carried out through a questionnaire including sensory, psychological and social aspects of pain. The sample consisted of 17 women (60.7%) and 11 men (39.3%) with an average age at the time of treatment of 59 ± 11 years. The average pain relief calculated from the NRS scores was 30.2 ± 21.4%, and the mean duration of pain relief was 10 ± 6 weeks. Pain intensity (p < 0.001), pain relief (p < 0.003) and mobility (p < 0.003) were all significantly improved after administration of lignocaine intravenous infusion therapy. Pain was significantly reduced in a group of osteoarthritis patients after administration of intravenous lignocaine. This suggests that part of the pain mechanism in this patient group may be neuropathic, appears to contribute significantly to the patients' pain, and requires further investigation in studies designed specifically for the purpose.

Randomised, double-blind controlled trial by dose reduction of implanted intrathecal morphine delivery in chronic non-cancer pain.

OBJECTIVE: This study aimed to investigate the efficacy of intrathecal morphine in the long term by hypothesising that a reduction of the intrathecal opioid dose following long-term administration would increase the level of pain intensity. DESIGN: Randomised, double-blind, controlled, parallel group trial. SETTING: Department of Pain Management, Russells Hall Hospital, Dudley, UK. PARTICIPANTS: 24 patients with non-cancer pain implanted with morphine reservoirs were assessed for eligibility. INTERVENTIONS: Participants were randomly allocated to one of two parallel groups in which one of the groups had no change in morphine dose and the other group had a small reduction (20%) in dosage every week during a 10-week follow-up. OUTCOME: Primary outcomes were visual analogue scale (VAS) pain score change and withdrawal from the study due to lack of efficacy. RESULTS: 9 of the patients assessed for eligibility declined to participate in the study. 15 patients were randomised to control (n=5) or intervention (n=10) and included in an intention-to-treat analysis. Owing to worsening of pain, seven patients withdrew from the study prematurely. None knew prior to withdrawal which arm of the study they were in, but all turned out to be in the dose-reduction arm. The calculation of dropout rates between groups indicated a significant statistical difference (p=0.026) and recruitment was ceased. The VAS change between baseline and the last observation was smaller in the control group (median, Mdn=11) than in the intervention group (Mdn=30.5), although not statistically significant, Z=-1.839, p=0.070; r=-0.47. Within groups, VAS was significantly lower at baseline (Mdn=49.5) than at the last observation (Mdn=77.5) for the reduction group, Z=-2.805, p=0.002; r=-0.627 but not for the control group (p=0.188). CONCLUSIONS: This double-blind randomised controlled trial of chronic intrathecal morphine administration suggests the effectiveness of this therapy for the management of chronic non-cancer pain. However, owing to the small number of patients completing the study (n=8), further studies are warranted. TRIAL REGISTRATION: International Standard Randomised Controlled Trials Centre (ISRCTN 33733462).

A narrative review of the impact of disbelief in chronic pain.

Although the experience of being believed is frequently alluded to in chronic pain literature, few studies have specifically explored this phenomenon and even fewer reviews have been offered. This narrative review sought to explore the wider social context in which individuals with chronic pain may experience disbelief toward their pain. Articles were obtained through a search of eight databases and a hand search of the references of full-text papers. Key results within the articles were noted and integrated to form three main themes: stigma, the experience of isolation, and the experience of emotional distress. The experience of stigma can occur in a number of ways. It may be through actual or perceived encounters with others; it can be through the use of psychologic explanations of pain; it can come through a perceived challenge to one's integrity and subsequently affect an individual's identity; and such stigma may be influenced by negative female stereotypes. The loss of relationships associated with being disbelieved can lead to the experience of isolation. This may be self-initiated, particularly when an individual has been given a contested diagnosis. Finally, disbelief can lead to emotional distress. This can take the form of guilt, depression, and anger. Throughout the article, implications for health care professionals, working with individuals living with chronic pain, are discussed.

Hypogonadism and low bone mineral density in patients on long-term intrathecal opioid delivery therapy.

OBJECTIVES: This study aimed to investigate the hypothalamic-pituitary-gonadal axis in a sample of male patients undertaking intrathecal opioid delivery for the management of chronic non-malignant pain and the presence of osteopaenia and/or osteoporosis in those diagnosed with hypogonadism. DESIGN: Observational study using health data routinely collected for non-research purposes. SETTING: Department of Pain Management, Russells Hall Hospital, Dudley, UK. PATIENTS: Twenty consecutive male patients attending follow-up clinics for intrathecal opioid therapy had the gonadal axis evaluated by measuring their serum luteinising hormone, follicle stimulating hormone, total testosterone, sex hormone binding globulin and calculating the free testosterone level. Bone mineral density was measured by DEXA scanning in those patients diagnosed with hypogonadism. RESULTS: Based on the calculated free testosterone concentrations, 17 (85%) patients had biochemical hypogonadism with 15 patients (75%) having free testosterone <180 pmol/L and 2 patients (10%) between 180 and 250 pmol/L. Bone mineral density was assessed in 14 of the 17 patients after the exclusion of 3 patients. Osteoporosis (defined as a T score ≤-2.5 SD) was detected in three patients (21.4%) and osteopaenia (defined as a T score between -1.0 and -2.5 SD) was observed in seven patients (50%). Five of the 14 patients (35.7%) were at or above the intervention threshold for hip fracture. CONCLUSIONS: This study suggests an association between hypogonadism and low bone mass density in patients undertaking intrathecal opioid delivery for the management of chronic non-malignant pain. Surveillance of hypogonadism and the bone mineral density levels followed by appropriate treatment may be of paramount importance to reduce the risk of osteoporosis development and prevention of fractures in this group of patients.

Prevalence and influence of diagnostic criteria in the assessment of hypogonadism in intrathecal opioid therapy patients.

BACKGROUND: Hypogonadism is frequently diagnosed based on total testosterone (TT) levels alone. However, 99% of testosterone is bound to the sex hormone-binding globulin (SHBG) with only 1% free testosterone. Alternative assessment methods consist of assay of free testosterone (FT) or bioavailable testosterone (BT) by equilibrium dialysis, calculation of FT and BT through the Vermeulen equations, and calculation of the free androgen index (FAI). OBJECTIVES: The aim of this study was to investigate the prevalence of hypogonadism in male chronic non-cancer pain patients undertaking long-term intrathecal opioid therapy and the existence of diagnostic discrepancies according to the criteria used. STUDY DESIGN: Prospective observational study. SETTING: Department of Pain Management, Russells Hall Hospital, Dudley, United Kingdom. METHODS: Twenty consecutive male patients undertaking long-term intrathecal opioid therapy had the gonadal axis evaluated by assays of luteinising hormone (LH), follicle stimulating hormone (FSH), TT, SHBG and by calculating the FT, BT and FAI. RESULTS: Hypogonadism was present in 17 (85%) of the patients based on TT; 17 (85%) according to FT and BT calculations; and 14 (70%) when calculating FAI. Based on either TT or FT being low or borderline/low, 19 (95%) of the investigated patients were biochemically hypogonadal. Significant differences were observed between diagnosis based on FT and FAI (P < 0.05). No significant differences were observed between diagnosis based on TT and FT (P = 0.40) or TT and FAI (P = 0.20). CONCLUSION: Hypogonadism is common in patients undertaking intrathecal opioid therapy for the management of chronic non-malignant pain; however, diagnostic criteria can influence the diagnosis of this side effect. The assessment of the hypothalamic-pituitary-gonadal axis should include evaluation of total serum testosterone, free testosterone, or bioavailable testosterone.

A predictive model for intrathecal opioid dose escalation for chronic non-cancer pain.

BACKGROUND: Tolerance is defined as a phenomenon in which exposure to a drug results in a decrease of an effect or the requirement of a higher dose to maintain an effect. The fear of a patient developing opioid tolerance contributes regularly to the stigmatization and withholding of intrathecal opioid therapy for chronic pain of non-cancer origin. OBJECTIVES: The aim of this study was to describe the intrathecal opioid dose escalation throughout the years in chronic non-cancer pain patients. A secondary objective was the development of an intrathecal opioid dose predictive model. STUDY DESIGN: Retrospective assessment of medical records. SETTING: Department of Pain Management, Russells Hall Hospital, Dudley, United Kingdom. METHODS: Medical records were reviewed and pump refill notes screened from the date of implant through November 2010 for 31 patients undertaking continuous intrathecal opioid therapy. All the patients included had undertaken a minimum of 6 years of intrathecal therapy when the data were collected. RESULTS: Significant increases in the intrathecal morphine dose were verified between follow-up at one year and all subsequent observations, F (2.075, 62.238) = 13.858, 0 < 0.001, but ceased to be significant from year 3 onwards, indicating stability of the morphine dose, F (3, 90) = 2.516, P = 0.63. A model that accounts for 76% of the variability of morphine doses at year 6 based on year 2 assessment combined with duration of pain prior to initiation of intrathecal therapy was developed: year 6 dose = -0.509 + (1.296 x [year 2 dose]) + (0.061 x [duration of pain]). LIMITATIONS: Retrospective study. CONCLUSION: The opioid dose escalation observed throughout the years was modest and not significant following year 3 of therapy. The model developed has the potential to assist the physician in the identification of a need for alternative treatment strategies. Furthermore, since many of the pump replacements are performed prior to year 6, it can also assist in the informed decision of the benefits and risks of the maintenance of this therapy.

Long-term intrathecal drug administration for chronic nonmalignant pain.

BACKGROUND: Chronic pain of nonmalignant origin requires effective long-term treatments, as for many patients pain management will be necessary throughout the rest of their lives. Intrathecal drug delivery systems (IDDS) have become a recognized therapy for the management of severe and otherwise intractable chronic pain. However, it is still not clear whether this treatment can be effective for periods up to 10 years or longer, given the paucity of long-term follow-up. This study sought to examine the effectiveness of IDDS following an average of 13 years postimplantation. METHODS: Twenty patients participated in a longitudinal study with an average follow-up of 13.5 years (range: 10.4 to 17.9) after IDDS implantation. Investigation was carried out by means of a questionnaire before IDDS and after an average of 4 and 13 years of IDDS therapy. Assessment of pharmacological data and complications/side effects was performed. RESULTS: Statistically significant improvements between baseline and 4-year assessment were observed for the following sensory and psychosocial variables: pain intensity, pain relief, coping, self-efficacy, depression, quality of life, housework, mobility, sleep, and social life (all P<0.001). No statistically significant changes were detected between assessments at averages of 4 and 13.5 years. CONCLUSIONS: This study, with one of the longest follow-up intervals reported in the IDDS literature, shows that IDDS has the potential to be a life-long pain management solution in appropriately selected patients with chronic nonmalignant pain.

Intrathecal granuloma formation as result of opioid delivery: systematic literature review of case reports and analysis against a control group.

OBJECTIVE: To investigate the existence of an association between formation of catheter tip intrathecal inflammatory masses with opioid dose and/or concentration. METHODS: A systematic review of catheter tip granulomas case reports and comparison with a control group was carried out. A boolean search was conducted in the electronic databases MEDLINE and EMBASE. The patients' data extracted from the case reports was tested for homogeneity with a control group. Subsequent analysis investigating the association of opioid dose, concentration and flow rate with the formation of catheter tip granulomas was performed. RESULTS: Seventeen articles resulting in 24 patients with granulomata were included in the review. One patient in our department with granuloma formation was added to this group. Control group comprised 31 patients with an average follow-up of 68.3±9.7 months. The groups were homogeneous considering the variables age, gender and duration of pain previous to implant. Morphine dose (r=0.821, p<0.001) and concentration (r=0.650, p<0.001) were significantly correlated with the development of catheter tip intrathecal masses. CONCLUSION: Opioid dose and concentration were significantly associated with the development of catheter tip granulomas. A correlation with opioid concentration was confirmed for the first time.

Randomized double-blind sham-controlled crossover study of short-term effect of percutaneous electrical nerve stimulation in neuropathic pain.

BACKGROUND: Percutaneous electrical nerve stimulation (PENS) is an electrical neuromodulation technique that has shown its therapeutic potential in various chronic pain conditions over the past few years, but well-blinded controlled studies are lacking. PATIENTS AND METHODS: A randomized double-blind sham-controlled crossover trial on 31 patients with chronic pain with surface hyperalgesia to investigate the efficacy of PENS. RESULTS: For the active PENS therapies, the median numerical rating scale (NRS) for pain changed from 7.5 (standard deviation [SD] ± 1) (range 6-10) before therapy to 0.5 (range 0-8.5) after therapy (Z = -4.206, P < 0.0005 [two-tailed]). The mean pain pressure threshold (PPT) measured with the von Frey aesthesiometer changed from 202 gm (SD ± 137 gm) (range 55-800 gm) before therapy to 626 gm (SD ± 228 gm) (range 45-800 gm) after therapy (Z = -4.373, P < 0.0005 [two-tailed]). There was a statistically significant difference between the changes in NRS for the active (3.9 [±3.2][0-8]) compared with the sham (0.1 [±0.4][0-1.5]) therapies, U = 40, Z = -3.484, P < 0.0001 (two-tailed). There was a statistically significant difference between the changes in PPT for the active (310 gm [±267 gm][0-670 gm]) compared with the sham (8 gm [±4 gm][0-15 gm]) therapies, U = 48.5, Z = -2.699, P = 0.007 (two-tailed). CONCLUSION: PENS therapy appears to be effective in providing short-term pain relief in chronic pain conditions. Studies, involving larger sample sizes and longer follow-up are recommended.

Intrathecal inflammatory masses: is the yearly opioid dose increase an early indicator?

OBJECTIVES: The objective of this study is to investigate the association between intrathecal drug, flow rate, drug concentration, and drug dose with the formation of intrathecal inflammatory masses. METHODS: A retrospective longitudinal study of 56 consecutive patients receiving long-term intrathecal analgesic administration was undertaken through screening of medical records. Data regarding drug flow rate, dose per day, and concentration of drugs administered were recorded for morphine, diamorphine, bupivicaine, clonidine and baclofen and averages computed. RESULTS: The average follow-up time post-implant was 91 ± 55 months (range: 9-209). Four of the 56 patients were diagnosed with intrathecal granuloma indicating a rate of 7%, the equivalent to 0.009 events per patient year. Twenty-one of the patients had received morphine either alone or combined; 22 had received diamorphine either alone or mixed; and 13 crossed over from morphine to diamorphine or the inverse. None of the patients with granuloma crossed over before diagnosis. A significant correlation was found between opioid dose (r= 0.275, p < 0.05), yearly increase of the opioid dose (r= 0.433, p < 0.05), and granuloma formation. Clonidine appeared to have a protective effect for the non-granuloma patients. No association was found with flow rate (r= 0.056) or opioid concentration (r= 0.214). CONCLUSION: This is the first detailed study showing an association of diamorphine with granulomas. This study supports the previous finding of intrathecal opioid dose being a risk factor for intrathecal granulomas and clonidine being protective. In addition we have found that the yearly increase in opioid dose is a risk factor for granulomas and could serve as an indicator for closer surveillance.

Stability and Analgesic Efficacy of Di-acetyl Morphine (Diamorphine) Compared with Morphine in Implanted Intrathecal Pumps In Vivo.

The objective of this study was to investigate di-acetyl morphine as an alternative opioid analgesic for use in implanted intrathecal drug delivery systems because of its greater solubility through evaluation of its stability in vivo and analgesic efficacy in the period between pump refills. Contents of intrathecal drug delivery system reservoirs (SynchroMed, Medtronic, Inc., Minneapolis, MN) that had been filled with di-acetyl morphine dissolved in saline (21), bupivacaine (9), or in both bupivacaine and clonidine (19) were sampled in vivo between 1 and 125 days after refill. The samples were assayed for di-acetyl morphine and its breakdown products by micellar electrokinetic capillary chromatography. Prospective daily numerical pain scores between pump refills, using 11-point Likert scales, on 24 patients with implanted SynchroMed pumps (12 delivering di-acetyl morphine in saline, 12 were delivering morphine in saline) were collected. Results showed that di-acetyl morphine immediately started to decay to mono-acetyl morphine in implanted Synchromed pumps with half-life of 50 days. Mono-acetyl morphine decayed to morphine with a maxima estimated at 125 days. There was no clinically significant change in average weekly pain scores for up to ten weeks in either group (range, 2.5 to 2.8 for diamorphine and 2.7 to 3.1 for morphine) (2-way repeated ANOVA, F(9,220) = 0.98, n.s.). We conclude that di-acetyl morphine and its breakdown products, 6 mono-acetyl morphine and morphine, provide similar analgesia to morphine alone when administered by intrathecal pump for a period of at least ten weeks and may be a useful alternative when a more soluble agent is favored.

Multiple lead spinal cord stimulation for chronic mechanical low back pain: a comparative study with intrathecal opioid drug delivery.

The objective of this paper is to assess the outcome of implanted multiple thoracolumbar lead spinal cord stimulation (SCS) in mechanical back pain without prior spinal surgery. These results are compared with intrathecal opioid drug delivery (ITDD). An anonymous third party patient questionnaire study of pain relief, function and psychosocial quality of life measures (recorded on 11-point numerical rating scales) for 12 patients with SCS and 13 with ITDD was used. Pain was significantly reduced with multiple lead SCS from a median of 9.0-6.5 (p < 0.01) and with ITDD from a median of 8.5-5.5 (p < 0.01). There was a trend towards greater reduction in pain in the ITDD group compared with the SCS group (pain differences 4.5 and 2.6, respectively) but this did not reach statistical significance. The majority of psychosocial quality of life measures were significantly more improved in the ITDD group compared with the SCS group (p < 0.05). We conclude that multiple-lead SCS improves mechanical back pain in patients unresponsive to more conservative measures. However, ITDD provides significantly more improved quality of life measures, with a trend towards greater pain reduction than SCS.