Antonella Paladini

Epidural Local Anesthetic Plus Corticosteroid for the Treatment of Cervical Brachial Radicular Pain: Single Injection Versus Continuous Infusion

BackgroundEfficacy of epidural local anesthetics plus steroids for the treatment of cervicobrachial pain is uncertain. MethodsA prospective study randomized 160 patients with cervicobrachial pain resistant to conventional therapy. Patients were divided into 4 groups on the basis of the time between pain onset and treatment initiation: group A, 40 patients with pain onset 15 to 30 days; group B, 40 patients with pain from 31 to 60 days; group C, 40 patients, 61 to 180 days; and group D, 40 patients with pain >180 days. Patients of each group were randomized to receive an epidural block with bupivacaine and methylprednisolone at intervals of 4 to 5 days (Single injection) or continuous epidural bupivacaine every 6, 12, or 24 hours plus methylprednisolone every 4 to 5 days (Continuos epidural). The maximum duration of treatment (9 blocks in Single injection, and 30 days in Continuos epidural) was dependent on achieving Pain Control (PC) ≥80% [PC is defined by this formulae: (100) (VASinitial−VASfinal)/VASinitial]. Follow-up at 1 month and 6 months compared PC and the number of pain-free hours of sleep. ResultsOne hundred forty-one patients completed the study. The 4 groups had similar characteristics. At the 1-month and 6-month follow-up analysis based on the time between pain onset and treatment initiation showed that patients of group D, who received the Continuous epidural treatment, had significantly greater PC and significantly more pain-free hours of sleep compared with similar patients in Single injection. ConclusionsTherapy with continuous epidural local anesthetic and methylprednisolone provides better control of chronic cervicobrachial pain compared with Single injection. These results are discussed with respect to the possible mechanism of action of the drugs and may relate to the physiopathologic mechanisms associated with neuronal plasticity that result in chronic pain.

Clonidine for treatment of postoperative pain: a dose-finding study.

The aim of this double‐blind randomized study was to evaluate the optimal intravenous dose of Clonidine administrated during the peri‐operative period, after lumbar hemilaminectomy for herniated disk repair. The ‘optimal intravenous dose’ was defined as that providing minimal analgesic request, stable haemodynamic profile and a minimal sedation score during 12 h after extubation. Eighty adult patients, ASA physical status I–II, undergoing lumbar hemilaminectomy for herniated disk (L4‐L5, L5‐S1) were included in the study. All the patients were randomly assigned to one of four study groups (A, B, C, D), 20 patients each. The same standardized general anaesthesia was performed for each group. Thirty minutes before the end of surgery, group A, B and C patients received three different loading doses of intravenous Clonidine (5 μg/kg, 3 μg/kg, 2 μg/kg respectively), followed by the same infusion of intravenous Clonidine (0.3 μg/kg per hour). Group D patients received a bolus dose and a continuous infusion of NaCl 0.9%. In the recovery unit, postoperative pain was treated by a patient‐controlled analgesia device, containing morphine. Pain relief was evaluated by the total morphine requirement during the postoperative period. Systolic blood pressure (SBP), heart rate and sedation were also noted during the first 12 h postoperatively. Intravenous Clonidine decreased morphine requirements in a dose‐dependent manner. Group A, B, C and D patients requested 5 ± 2, 11 ± 3, 19 ± 4 and 29 ± 8 doses of morphine respectively. Clonidine also affected SBP in a dose‐related manner. Group A, B and C patients had an SBP decrease respectively of 26 ± 3%, 7 ± 4% and 2 ± 2% compared with basic values while, at the same time, in group D patients no SBP variation was registered. In conclusion, this study demonstrates that, when sedation and analgesic effect of Clonidine is required, 3 μg/kg bolus dose followed by a continuous infusion of 0.3 μg/kg per hour has to be considered the optimal intravenous dose. The higher dose of intravenous Clonidine (5 μg/kg) produced better analgesia but the degree of hypotension and sedation was more severe and longer lasting; it required ephedrine administration and careful monitoring of the patient. On the other hand, the bolus of intravenous Clonidine 2 μg/kg (group C) was less effective in terms of pain relief but with similar side‐effects to the 3 μg/kg dosage (group B).

Acute Pain and Availability of Analgesia in the Prehospital Emergency Setting in Italy: A Problem to be Solved

Objectives:  The treatment of acute pain in the prehospital emergency setting remains a significant problem. We evaluated the incidence, site, and possible cause of acute pain in the prehospital period and also the current state of prehospital pain management by evaluating analgesic availability in emergency vehicles in Italy.

Improved Cancer Pain Treatment Using Combined Fentanyl‐TTS and Tramadol

▪ Abstract:  The aim of the study was to facilitate dose escalation of strong opioids. In this randomized open‐label study the influence of tramadol on dose adjustment of transdermal fentanyl in advanced cancer pain control was prospectively evaluated. Seventy patients affected by intractable cancer disease with visual analog scale (VAS) score >3 were enrolled. Thirty‐five patients were treated conventionally with increasing transdermal fentanyl dosage as required (group F) and 35 patients received oral tramadol added to their transdermal fentanyl before each increment of the transdermal opioid dosage (group T). Pain control was equally satisfactory in the two groups. VAS scores at baseline (T: 4.36 ± 1.53; F: 4.51 ± 1.36; n.s.) and at the end of the study (T: 1.8 ± 1.6; F: 1.6 ± 1.5; n.s.) did not differ. However, in the tramadol group this level of pain control was achieved with much slower dose escalation of fentanyl. The mean application time of the fentanyl‐Transdermal Therapeutic System patch for each dosage (25, 50, 75 μg/hour) was significantly greater in patients receiving tramadol. No patient in group T escalated to the 100 μg/hour patch, while in 12 patients of group F the 100 μg/hour patch was applied after a 75 μg/hour patch mean application period of 18.6 ± 4.7 days. The number of fentanyl‐TTS dosage changes was significantly lower in group T (1.2 ± 0.4 vs. 2.3 ± 0.5; P < 0.05). The mean total duration of treatment in group T, was 37.1 ± 11.6 days. The amount of fentanyl used at study end was 56.6 ± 11.2 μg/hour plus 141.1 ± 151.9 mg tramadol per day (median: 200 mg/day) in group T patients compared with 84.1 ± 12.2 μg/hour in group F patients (P < 0.05). The combination of a strong opioid with a weak opioid to treat severe cancer pain allowed a more gradual increase of analgesic delivery than was possible using fentanyl‐TTS alone, minimizing periods of under‐ and overdosing. In addition, it considerably slowed the pace of fentanyl dose escalation. In conclusion, this TTS fentanyl‐tramadol analgesic protocol provides a useful alternative to the usual treatment of cancer pain with fentanyl‐TTS alone, especially in case of quick progression of disease and pain. ▪

Transdermal Buprenorphine for Central Neuropathic Pain: Clinical Reports

Transdermal buprenorphine is an effective analgesic for a variety of pain conditions. Traditionally, neuropathic pain is treated with medications such as tricyclic antidepressants or anticonvulsants, with opioid medications as second or third‐line agents. We present two different painful conditions of presumed neuropathic origin, with complex etiopathogenesis, which were successfully treated with buprenorphine. The results of treatment of these neuropathic pain syndromes with buprenorphine are encouraging, suggesting that it might represent a valid alternative to standard approaches for central neuropathic pain.

Neural modulation by blocks and infusions.

Abstract:  Neural blockade is widely used in clinical practice to alleviate acute or chronic pain, including neuropathic pain. However, to date there is little controlled evidence to confirm the efficacy of nerve blocks in neuropathic pain. The most common indication for nerve blocks, especially sympathetic blockade, is complex regional pain syndrome, in which success rates of up to 38% have been achieved, depending on the type of the block used. Greater efficacy has been achieved by combining a nerve block with patient‐controlled analgesia. Sympathectomy is recommended for the treatment of neuropathic pain only after careful consideration of its usefulness, effectiveness, and risk of adverse effects. Current evidence and clinical experience suggest that neural blockade could be a useful adjunct in the management of refractory neuropathic pain, but further well‐controlled studies would be of great benefit to support this type of therapy.

Depression and chronic pain in the elderly: links and management challenges

Aging is an inevitable process and represents the accumulation of bodily alterations over time. Depression and chronic pain are highly prevalent in elderly populations. It is estimated that 13% of the elderly population will suffer simultaneously from the two conditions. Accumulating evidence suggests than neuroinflammation plays a critical role in the pathogenesis of both depression and chronic pain. Apart from the common pathophysiological mechanisms, however, the two entities have several clinical links. Their management is challenging for the pain physician; however, both pharmacologic and nonpharmacologic approaches are available and can be used when the two conditions are comorbid in the elderly patients.

New and Low‐Cost Auto‐Algometry for Screening Hypertension‐Associated Hypoalgesia

Objective:  The aim of the present work was to measure the pain threshold in hypertensive patients with a new auto‐algometry method.

Strong analgesics: Working towards an optimal balance between efficacy and side effects

Inadequately treated chronic pain remains a major cause of suffering. A recent survey found that moderate to severe chronic pain affects 19% of adult Europeans (Breivik et al., 2006). Other large scale surveys in Australia (Blyth et al., 2001), Denmark (Sjogren et al., 2009) and Norway (Rustoen et al., 2004) have given similar results. These also represent a substantial socioeconomic burden (Dunn and Croft, 2004). Moreover, these surveys may underestimate the true incidence, because many patients paradoxically report their analgesia to be satisfactory despite being in pain. One study found that over 75% of patients declared themselves satisfied or very satisfied with their overall pain management, despite almost 50% reporting recent moderate to severe pain (Dawson et al., 2002). The cornerstone of treatment for moderate to severe pain is classical opioid therapy; the WHO Pain Analgesic Ladder recommends weak opioids for Step 2 and strong opioids for Step 3 in the management of chronic pain (WHO, 1996), even if this recommendation has been criticized (Marinangeli et al., 2004). However, the prescription of opioids is still limited by medical, ethical, cultural and legal issues (Bhamb et al., 2006; Jacobsen et al., 2007). One major factor is opiophobia; physicians’ and patients’ concerns about the appropriate use of opioids, and their fears and misunderstandings in connection with these agents. Patients may be reluctant to take opioids because of a perceived association with drug abuse and criminality (Fields, 2007) or with terminal illness. Classic opioid therapy also has shortcomings; specifically, in providing sustained analgesic efficacy over long periods, reliable efficacy in difficult-to-treat pain syndromes, and acceptable levels of tolerability. Balancing adequate pain relief with minimal side effects is difficult, and sometimes impossible. Long term opioid efficacy may be compromised by the development of tolerance and/or hyperalgesia. The current clinical strategy for managing these phenomena is opioid rotation, utilising the incomplete cross-tolerance between opioids in order to recover efficacy (DuPen et al., 2007). However, the evidence for this strategy is largely anecdotal or based on observational and uncontrolled studies, and there are no predictive criteria for the best drug option. A recent approach has been to combine drugs with different modes of action, such as morphine with N-methyl-D-aspartate (NMDA) antagonists, anticonvulsants or antidepressants. A few clinical studies have been undertaken with morphine plus the NMDA antagonist dextromethorphan. The combination has so far failed to demonstrate either enhanced opioid analgesia or reduced tolerance compared to morphine alone, and – in addition – discontinuation rates have been higher with the combination (Galer et al., 2005). Difficult-to-treat pain syndromes are essentially those where the pain is neuropathic in origin or has a neuropathic component. Examples include diabetic peripheral neuropathy, post-herpetic neuralgia and mixed cancer pain. Many different drugs are currently used to treat these syndromes and there is no gold standard for treatment, demonstrated by a review of 105 high-quality, randomised, placebo-controlled clinical trials (Finnerup et al., 2005). Experienced pain therapists use a combination of analgesics (often an opioid and a non-opioid) with different modes of action. Animal studies have suggested that combining morphine with an alpha2 delta ligand such as gabapentin (Matthews and Dickenson, 2002), a tricyclic antidepressant such as amitriptyline (Luccarini et al., 2004), or an NMDA antagonist such as ketamine (Pelissier et al., 2003) all offer some benefit. However, some unresolved issues remain with this approach (such as the safety of polypharmacy and its effect on compliance), while clinical trials suggest that any improvement in efficacy may be outweighed by the increased incidence of side effects (Hanna et al., 2008; Gilron et al., 2005). Tolerability problems are common with opioids, particularly nausea and vomiting during the first one or two weeks, and constipation throughout long term treatment. Anti-emetics and laxatives may be used both for prophylaxis and treatment of these adverse events, but the current pharmacological approach is often unsatisfactory and/or the regimen is too complex, so patients discontinue treatment because of additional and intolerable side effects. One recent alternative is to combine a classical opioid with a systemic mu opioid receptor antagonist (Muller-Lissner et al., 2007), but further studies are needed. Peripheral selective and non-selective mu opioid receptor antagonists have been developed. These act on peripheral receptors, including those located within the GI tract, and do not cross the blood–brain barrier. Some clinical trials has shown that subcutaneous methylnaltrexone rapidly induces laxation in patients with advanced illness and opioid-induced consti-

Low Back Pain in a Natural Disaster

Low back pain is usually self‐limited. The transition from acute to chronic LBP is influenced by physical and psychological factors. Identification of all contributing factors, in a mass emergency setting, differentiating primary and secondary life‐threatening forms of LBP, is the best approach for success. Aims of the present report were to estimate the prevalence of LBP in population afferent to four advanced medical presidiums (AMPs) during postseismic emergency period and to evaluate frequency of use, types of pain killers administered to patients and short‐term efficacy of them.