William Raffaeli

An opposite-direction modulation of the COMT Val158Met polymorphism on the clinical response to intrathecal morphine and triptans.

UNLABELLED Genetic variation in the COMT gene is thought to have clinical implications for pain perception and pain treatment. In the present study, we first evaluated the association between COMT rs4680 and the analgesic response to intrathecal morphine in patients with chronic low back pain to provide confirmation of previously reported positive findings. Next, we assessed the relationship between rs4680 and headache response to triptans in 2 independent cohorts of migraine patients. In patients with chronic low back pain (n = 74), logistic stepwise regression analysis showed that age (odds ratio [OR]: .90, 95% confidence interval [CI]: .85-.96, P = .002) and the presence of the COMT Met allele (vs Val/Val, OR: .21, 95% CI: .04-.98, P = .048) were predictive factors for lower risk of poor analgesic response to intrathecal morphine. Intriguingly, in migraine patients, the COMT rs4680 polymorphism influenced headache response to triptans in the opposite direction. Indeed, in an exploratory cohort of migraine patients without aura (n = 75), homozygous carriers of the COMT 158Met allele were found at increased risk to be poor responders to frovatriptan when compared to homozygous patients for the Val allele (OR: 5.20, 95% CI: 1.25-21.57, P = .023). In the validation cohort of migraine patients treated with triptans other than frovatriptan (n = 123), logistic stepwise regression analysis showed that use of prophylactic medications (OR: .43, 95% CI: .19-.99, P = .048) and COMT Met/Met genotype (vs Val/Val, OR: 4.29, 95% CI: 1.10-16.71, P = .036) were independent risk factors for poor response to triptans. PERSPECTIVE This study highlights the importance of COMT rs4680 in influencing the clinical response to drugs used for chronic pain, including opioid analgesics and triptans. These findings also underline a complex relationship between COMT genotypes and pain responder status.

Long-term intrathecal morphine and bupivacaine upregulate MOR gene expression in lymphocytes

BACKGROUND Several studies have shown that opioids may suppress the immune system either by binding to mu-opioid receptors (MOR) expressed in immune cells or by activating these receptors within the central nervous system. OBJECTIVE To assess the level of lymphocyte expression of MOR mRNA in patients with chronic non-cancer pain, who were treated with intrathecal morphine or with morphine plus bupivacaine via an intrathecal drug delivery system, and to investigate whether intrathecal morphine and the associated local anesthetic administration influences lymphocyte subpopulations. METHODS In total, 29 people [10 controls (age range 59-85 years) and 19 patients (age range 47-89 years) with various chronic non-malignant pain conditions] were enrolled in the study. MOR mRNA levels were evaluated in peripheral lymphocytes, and lymphocyte subsets were determined by direct immunofluorescence using flow cytometry. RESULTS After 12 months of treatment with intrathecal morphine (1.5-4 mg/day), there was an increase in MOR mRNA levels in lymphocytes of 65% compared with controls and 47% with pretreatment values. Even higher levels (increase of 142% compared with controls and 135% with pretreatment values) were observed in the patients treated with morphine plus bupivacaine (0.2-0.4 mg/day). Elevation of MOR mRNA levels was confirmed in patients after 24 months of treatment. At this time point, the percentage of natural killer cells was significantly decreased. CONCLUSION This preliminary study suggests that opioids must be used with care in patients who are already immunosuppressed by disease or by other, concurrently administered drugs.

Implantable Intrathecal Pumps for the Treatment of Noncancer Chronic Pain in Elderly Population: Drug Dose and Clinical Efficacy

Objective.   This study aims to assess long‐term follow‐up of efficacy and quality of life for 34 geriatric patients (10 men, 24 women, mean age 72.3 ± 11.6 years) with intrathecal (IT) drug delivery systems (IDDS), implanted between 1994 and 2002, for the treatment of severe noncancer chronic pain.

Population-based study of central post-stroke pain in Rimini district, Italy

Central post-stroke pain (CPSP) is still an underestimated complication of stroke, resulting in impaired quality of life and, in addition to the functional and cognitive consequences of stroke, the presence of CPSP may be associated with mood disorders, such as depression, anxiety, and sleep disturbances. This type of pain may also impair activities of daily living and further worsen quality of life, negatively influencing the rehabilitation process. The prevalence of CSPS in the literature is highly variable (1%–12%) according to different studies, and this variability could be influenced by selection criteria and the different ethnic populations being investigated. With this scenario in mind, we performed a population-based study to assess the prevalence of CPSP and its main features in a homogeneous health district (Rimini, Italy), including five hospitals for a total population of 329,970 inhabitants. From 2008 to 2010, we selected 1,494 post-stroke patients and were able to interview 660 patients, 66 (11%) of whom reported pain with related tactile and thermal hyperesthesia, accompanied by needle puncture, tingling, swelling, and pressure sensations. Patients reported motor impairment and disability, which influenced their working ability, rehabilitation, and social life. Despite this severe pain state, there was a high percentage of patients who did not receive adequate treatment for pain.

Illness Awareness in Hospice: Application of a Semi-Structured Interview:

This study describes the results of a semi-structured interview to assess the illness awareness of cancer patients in Hospice. The results of this study are based on the interviews made in Rimini and Savignano sul Rubicone Hospices (n = 51). Psychologists evaluated illness awareness of the participants interviewed independently from the code system that is provided for the interview. According to the psychologists, 18 patients (35%) were aware, 11 patients (22%) were unaware, and 22 patients (43%) were aware with defense mechanisms. According to the code system of the interview, the results were the following: 18 patients (35%) were aware, 2 patients (4%) were unaware, and 29 patients (57%) were aware with defense mechanisms. Two participants had to be reassessed because of inconsistency in some factors. In conclusion, the data analysis underlined that the congruence of the 2 assessment methods was found in 33 of the 51 patients examined (65%) and that the degree of concordance was rather low (κ = .46; 95% CI = 0.24-0.68).

Pain as a disease: an overview

The acknowledgment of pain as a pathologic entity in its own right remains debated. Notwithstanding the data showing the burden of pain as a disease, an ultimate recognition of the pathologic nature of this condition is lacking. In this study, we analyze the notion of pain as a disease through an historical overview of its several conceptualizations and report the main evidence supporting this notion. We believe that a clear definition of pain as a disease is necessary, especially considering the enormous global burden of this condition. Indeed, the recognition of pain as a definite pathologic state is crucial to raise awareness about this neglected global health problem and to promote the exploration of new specific therapeutic approaches.

High opioid dosage rapid detoxification of cancer patient in palliative care with the Raffaeli model.

BACKGROUND Chronic opioid administration can induce adverse drug-dependent events and tolerance and/or hyperalgesia development. Opioid rotation is the treatment option in this case; however, it can expose patients to long periods of ineffectiveness and/or development of withdrawal syndrome, overdose, or adverse events. To overcome this issue, a method of rapid detoxification from opioids has been developed. AIMS To assess feasibility and efficacy of our opioid detoxification protocol in patients affected from chronic cancer pain. SETTINGS/PATIENTS: We studied 15 patients, with chronic cancer pain, who were afferent to Hospice of Rimini, Italy, were in therapy with high doses of opioid and needed opioid rotation or a therapeutic variation because of opioid toxicity, inefficacy, tolerance, or hyperalgesia. Each patient received a fixed dose of endovenous morphine and clonidine plus oral ketoprofen or ibuprofen, and oral lorazepam, if required, for at least 3 days, suspending the previous opioid therapy. We monitored withdrawal symptoms, pain intensity, type, and intensity of adverse events. RESULTS Withdrawal symptoms were experienced by four (26.6 percent) patients. The average Numerical Rating Scale for pain decreased significantly (p < 0.05) from 8.3 ± 1.57 to 3.6 ± 1.4 at the end of the detoxification and to 2.4 ± 1 at the end of the rotation or therapeutic adjustment. Average duration of the detoxification was 6.86 ± 6.4 days (range 3-22). CONCLUSIONS The results suggested that the detoxification protocol may be effective in preventing withdrawal signs in patients needing a therapeutic change because of opioid-induced tolerance, hyperalgesia, or toxicity.

Caregiver Evaluation in Hospice Application of a Semi-Structured Interview

In this study we report the results of construction and administration of a semi-structured interview for the evaluation of caregivers in hospice. The results presented here are related to interviews (n = 25) that were administered at Rimini Hospice. According to the interview coding system, it was possible to identify thematic areas of the interviews where the caregiver’s distress was mainly concentrated. As concerning the care burden, greater distress was detected in areas relating to the change in the rhythm of life (38%) and in social network (26%); whereas, as concerning the psychological burden, a greater distress was detected in the area related to the caregiver role (51%). In conclusion, a singular element identified as a source of distress in, our study, is that of social network.

Qualitative Pain Classification in Hospice and Pain Therapy Unit

In this study, we investigated patients meaning attribution to pain in hospice and pain therapy unit, using a qualitative approach: narrative-based medicine. The data presented here were related to patients (n = 17) hospitalized in Rimini Hospice (Italy). These data were compared to those of patients (n = 21) with noncancer pain (control sample). The interviews were then analyzed according to the technique of thematic narrative analysis. The results of our research identified a differential process in pain processing in relationship to the meaning that the patient attributed to pain. The thematic analysis of the interviews allowed the inductive construction of a specific network of pain dimensions, which were summarized in “the pain chronogram.”

Epiduroscopy and radiofrequency technique: the Raffaeli–Righetti technique

Abstract Objectives: Periduroscopy has been re-evaluated only recently for the diagnosis, and especially the treatment, of complex rachidian pain, such as that due to the failed back surgery syndrome (FBSS). The classic periduroscopy procedure has major limitations in that it can only use liquids as a method to visualize the dura space, and cannot overcome fibrotic (partial or complete) obstructions of the channel. In order to overcome these limitations, we added two modifications to the classic procedure – the Raffaeli–Righetti technique. Patients and methods: A Fogarty balloon was used to clean the channel. This tool has allowed reduction by 50% of the volume of fluid used in the periduroscopy. The second innovation involves the use of the resaflex for the lysis of channel obstructions (fat and/or fibrotic tissues), which allows reaching the site of pain origin and improving the efficiency of the periduroscopy by 30%. The resaflex uses an electric wave to lyse tender tissues (lysing and coagulating at t...