An incoherent HIFU transducer for treatment of the medial branch nerve: Numerical study and in vivo validation.

BACKGROUND: Chronic back pain due to facet related degenerative changes affects 4-6 million patients a year in the United States. Patients refractory to conservative therapy may warrant targeted injections of steroids into the joint or percutaneous medial branch nerve denervation with radiofrequency ablation. We numerically tested a novel noninvasive high intensity focused ultrasound transducer to optimize nerve ablation near a bone-soft tissue interface. METHODS: A transducer with 4 elements operating in an incoherent mode was modeled numerically and tested pre-clinically under fluoroscopic guidance. After 6 lumbar medial branch nerve ablations were performed in 2 pigs, they were followed clinically for 1 week and then sacrificed for pathological evaluation. RESULTS: Simulations show that the acoustic spot size in water at 6 dB was 14mm axial x 1.6mm lateral and 52mm axial x 1.6mm lateral for coherent and incoherent modes, respectively. We measured the size of N = 6 lesions induced in vivo in a pig model and compared them to the size of the simulated thermal dose. The best match between the simulated and measured lesion size was found with a maximum absorption coefficient in the cortical bone adjusted to 30 dB/cm/MHz. This absorption was used to simulate clinical scenarios in humans to generate lesions with no potential side effects at 1000 and 1500 J. CONCLUSION: The elongated spot obtained with the incoherent mode facilitates the targeting during fluoroscopic-guided medial branch nerve ablation.

Development and Implementation of a Registry of Patients Attending Multidisciplinary Pain Treatment Clinics: The Quebec Pain Registry.

The Quebec Pain Registry (QPR) is a large research database of patients suffering from various chronic pain (CP) syndromes who were referred to one of five tertiary care centres in the province of Quebec (Canada). Patients were monitored using common demographics, identical clinical descriptors, and uniform validated outcomes. This paper describes the development, implementation, and research potential of the QPR. Between 2008 and 2013, 6902 patients were enrolled in the QPR, and data were collected prior to their first visit at the pain clinic and six months later. More than 90% of them (mean age ± SD: 52.76 ± 4.60, females: 59.1%) consented that their QPR data be used for research purposes. The results suggest that, compared to patients with serious chronic medical disorders, CP patients referred to tertiary care clinics are more severely impaired in multiple domains including emotional and physical functioning. The QPR is also a powerful and comprehensive tool for conducting research in a "real-world" context with 27 observational studies and satellite research projects which have been completed or are underway. It contains data on the clinical evolution of thousands of patients and provides the opportunity of answering important research questions on various aspects of CP (or specific pain syndromes) and its management.

Canadian recommendations for the management of breakthrough cancer pain.

Breakthrough cancer pain (btcp) represents an important element in the spectrum of cancer pain management. Because most btcp episodes peak in intensity within a few minutes, speed of medication onset is crucial for proper control. In Canada, several current provincial guidelines for the management of cancer pain include a brief discussion about the treatment of btcp; however, there are no uniform national recommendations for the management of btcp. That lack, accompanied by unequal access to pain medication across the country, contributes to both regional and provincial variability in the management of btcp. Currently, immediate-release oral opioids are the treatment of choice for btcp. This approach might not always offer optimal speed for onset of action and duration to match the rapid nature of an episode of btcp. Novel transmucosal fentanyl formulations might be more appropriate for some types of btcp, but limited access to such drugs hinders their use. In addition, the recognition of btcp and its proper assessment, which are crucial steps toward appropriate treatment selection, remain challenging for many health care professionals. To facilitate appropriate management of btcp, a group of prominent Canadian specialists in palliative care, oncology, and anesthesiology convened to develop a set of recommendations and suggestions to assist Canadian health care providers in the treatment of btcp and the alleviation of the suffering and discomfort experienced by adult cancer patients.

Methadone is safe for treating hospitalized patients with severe pain.

PURPOSE: Methadone is still regarded as a second line opioid for patients suffering from severe pain, and is rarely used in hospitalized patients. The infrequent use of methadone is probably due to its long plasma half-life that could lead to accumulation and toxicity. In the present study we report that clinically effective analgesic doses of methadone, given either epidurally or orally, can be used safely for prolonged treatment in hospitalized patients. CLINICAL FEATURES: Over a five-year period we administered methadone at Hadassah Hospital in Jerusalem to 3,954 in-patients with severe pain, 12% of whom were younger than 17 yr. Satisfactory pain relief was recorded in more than 85% of the patients. None of the patients treated with oral methadone developed serious side effects. Three patients, treated with epidural methadone (0.09%), developed a clinically significant respiratory depression. In all three cases, epidural pump failure or pump misprogramming resulted in methadone overdose. None of the children or adults treated with methadone developed addiction during hospitalization. CONCLUSION: Based on its analgesic properties and marked safety profile, we suggest that methadone could be added to the analgesic armamentarium of in-hospital health-care providers. Moreover, methadone could serve as the opioid of first choice in some in-patient populations.

Consumption of soy diet before nerve injury preempts the development of neuropathic pain in rats.

BACKGROUND: A previous report using a partial sciatic nerve ligation (PSL) model for neuropathic pain in rats demonstrated that consumption of soy-containing diets preoperatively and postoperatively suppressed development of mechanical and heat allodynia, as well as hyperalgesia. The current study examined whether dietary soy suppresses these neuropathic sensory disorders when consumed either before or after PSL injury. METHODS: Male Wistar rats were grouped into seven different feeding regimens. These rats were fed SOY (RMH-1000, PMI Feeds, St. Louis, MO), a diet containing 85% soy protein since weaning, and were then switched to noSOY (Bio-Serv Co., Frenchtown, NJ), a diet devoid of soy at certain time points before PSL injury (14, 7, 1 days, or 15 and 0 h). Postoperatively, these rats were fed SOY or noSOY diets. Levels of mechanical and heat allodynia and hyperalgesia were determined preoperatively and 3, 8, and 14 days after PSL injury. RESULTS: Compared with groups fed preoperative noSOY, consumption of SOY before PSL injury significantly blunted postoperative levels of allodynia and hyperalgesia. Administering the SOY diet both before and after PSL injury provided no additional suppression of neuropathic pain. No pain suppression was noted in rats fed a noSOY diet preoperatively and SOY diet after PSL injury. Switching from SOY to noSOY feeding within 15 h of PSL injury was sufficient to allow for the full development of allodynia and hyperalgesia. CONCLUSIONS: Consumption of a soy-containing diet suppressed the development of neuropathic pain after PSL injury. The pain-suppressing properties of dietary soy were the result of a preemptive effect (i.e., when consumed preoperatively), but not a palliative effect (i.e., when consumed postoperatively). This effect of soy-containing diets appears to be short-lived, since switching to a noSOY diet 15 h before ligation abrogated the suppressive effect of soy.

A randomized trial of fluoxetine versus amitriptyline in musculo-skeletal pain.

In a preclinical study we found fluoxetine alone to induce a serotonin-mediated, dose-dependent antinociceptive effect in the mouse hot plate assay. In the present study we evaluated the clinical implication of these findings, comparing the efficacy of fluoxetine with that of amitriptyline for musculo-skeletal pain. Forty non-depressed patients, suffering from low back pain and whiplash associated cervical pain were enrolled in a randomized, six-week, "blind-rater" study, comparing the analgesic effect of amitriptyline (50-75 mgs/day) with that of fluoxetine (20 mgs/day). Twenty patients were randomly assigned to the amitriptyline group, and twenty to the fluoxetine group. Visual analogue and verbal rating scales were used for the assessment of pain intensity and pain relief. Thirty-five patients concluded the study. Moderate or good relief of pain was reported by 14 of the 17 patients (82%) in the amitriptyline group, and by 14 of the 18 patients (77%) in the fluoxetine group. The difference in responses between amitriptyline and fluoxetine was not statistically significant. In our study, fluoxetine relieved low back pain and whiplash associated cervical pain with efficacy similar to that of amitriptyline, offering an alternative for patients unable to tolerate the tricyclic antidepressants' side effects.

Soy-containing diet suppresses chronic neuropathic sensory disorders in rats.

UNLABELLED: Partial sciatic nerve ligation (PSL) in rodents produces chronic neuropathic sensory disorders resembling neuropathic pain in humans. We previously reported that levels of allodynia and hyperalgesia after PSL injury were markedly attenuated by consumption of soy-containing diets. Here we aimed to show that dietary effect on pain behavior is not specific to a certain laboratory. For this purpose, experiments were conducted in a different laboratory (Baltimore rather than Jerusalem) and a different rat strain (Wistar rather than Sabra), with additional and different testing methods (radiant heat from a lamp rather than a CO(2) laser). Rats were fed two soy-free diets and a soy-containing one for 28 days. The sensitivity of rats to nonnoxious and noxious stimuli was determined before PSL injury, and levels of neuropathic sensory disorders were determined after it. We found that consuming the soy-containing diet prevented development of tactile and heat allodynia, but not mechanical hyperalgesia. This dietary effect was not correlated with calorie intake and weight gain or dietary concentration of fat and carbohydrates. We conclude that, regardless of experimental site, diet markedly affects chronic neuropathic sensory disorders in rats and should be standardized in animal models of pain. IMPLICATIONS: Levels of chronic sensory disorders in a rat model of allodynia and hyperalgesia after partial sciatic nerve ligation depend on the consumption of a soy-containing diet. Further studies are needed to determine the role of diet in humans with chronic pain.

Heat hyperalgesia following partial sciatic ligation in rats: interacting nature and nurture.

As in humans, levels of neuropathic pain produced by nerve injury are highly variable among animals. This variability was attributed to genetic and environmental factors. For example, we reported that chronic neuropathic sensory disorders developing following total (autotomy) or partial nerve injury (allodynia and hyperalgesia) depended on the diet rats consumed. Here we investigated the interaction between genetic and dietary factors in the development of heat hyperalgesia in rats following partial sciatic ligation (the PSL model). We show that heat sensitivity of intact rats and levels of heat hyperalgesia of PSL-injured rats were highly variable across eight different rat strains and seven different diets. Thus, genetic and environmental variables interact in determination of levels of chronic neuropathic sensory disorders in rats.

Correlation of intact sensibility and neuropathic pain-related behaviors in eight inbred and outbred rat strains and selection lines.

In some rat strains, total hindpaw denervation triggers autotomy, a behavior of self mutilation presumably related to neuropathic pain. Partial sciatic ligation (PSL) in rats produces tactile allodynia and heat hyperalgesia but not autotomy. Our aims in this study were to examine: (1) whether sensibility of intact rats to noxious and non-noxious stimuli is strain-dependent; (2) whether sensibility of intact rats could predict levels of autotomy, or of allodynia and hyperalgesia in the PSL model; and (3) whether autotomy levels are correlated with levels of allodynia or hyperalgesia. Here we report that in two inbred rat strains (Lewis and Fisher 344), two outbred rat strains (Sabra and Sprague-Dawley) and four selection lines of rats (Genetically Epilepsy-Prone Rats, High Autotomy, Low Autotomy and Flinders Sensitive Line), tactile sensitivity and response duration to noxious heat of intact animals were strain-dependent. Levels of autotomy following hindpaw denervation and of allodynia and hyperalgesia in the PSL model were also strain-dependent. Thus, these traits are determined in part by genetic factors. Sensory sensibility of intact rats was not correlated with levels of autotomy following total denervation, or allodynia and hyperalgesia following partial denervation. We suggest that preoperative sensibility of intact rats is not a predictor of levels of neuropathic disorders following nerve injury. Likewise, no correlation was found between autotomy, allodynia and hyperalgesia, suggesting that neuropathic pain behaviors triggered by nerve injury of different etiologies are mediated by differing mechanisms.

Dietary supplementation with the inhibitory amino acid taurine suppresses autotomy in HA rats.

Taurine is an inhibitory amino acid in the CNS. When supplied to rats it produces analgesia in some acute pain tests. Here we examined the effect of taurine supplementation on sensitivity to pain in intact rats, and whether perioperative dietary supplementation with taurine in rats would suppress autotomy, a behavior produced by peripheral neurectomy and related to neuropathic pain. Thermal pain sensitivity of intact rats consuming 1% taurine in the drinking solution for 2 weeks was not significantly different from that of control rats. Autotomy levels, determined in rats consuming taurine pre-, post- or perioperatively were significantly lower than in matching control groups. We conclude that taurine plays an important role in the autotomy model, presumably by protecting inhibitory neurons in the CNS against an excitotoxic damage triggered by injury discharge and ectopic input from the severed nerves.

Pain and quality of life following radical retropubic prostatectomy.

PURPOSE: We assess pain and quality of life following radical retropubic prostatectomy and determine whether intraoperative anesthetic management has any long-term effects on outcomes. MATERIALS AND METHODS: A total of 110 patients undergoing radical retropubic prostatectomy were randomly assigned to receive epidural and/or general anesthesia. Patients responded to a questionnaire mailed 3 and 6 months following surgery that assessed prostate symptoms, pain related to surgery, quality of life and mood. RESULTS: No long-term effects of anesthesia were observed. Of the 103 respondents (94%) at 3 months 49% had some pain related to surgery. Although pain was not related to anesthesic technique, patients who had it at 3 months used significantly more pain medication on postoperative day 3. Pain at 3 months was mild, averaging 1.5 on a scale of 0 to 10, and associated with poor perceptions of overall health (p <0.02), and reduced physical (p <0.01) and social (p <0.01) functioning. Pain at 3 months was associated with higher levels of preoperative anxiety (p <0.05). At 6 months 36 of 90 patients (35%) had some pain related to surgery and the impact was similar. CONCLUSIONS: Long-term effects of intraoperative anesthesic technique were not apparent. Mild pain following radical retropubic prostatectomy was common and associated with reduced quality of life, particularly social functioning. Affective distress, particularly anxiety, before surgery and use of pain medications following surgery may be predictors of chronic pain following radical retropubic prostatectomy.

Chronic diarrhea--induced by celiac plexus block?

A 59-year-old man had severe chronic diarrhea after a celiac plexus block. The block was performed because of unbearable abdominal pain caused by a benign cyst in the lesser sac. The patient also had diabetes mellitus and was treated with metformin. Thorough investigation and various therapeutic trials failed to detect the cause for the diarrhea or to improve it. Based on the temporal relationship we wonder whether the diarrhea was induced by the celiac block procedure. The relevant literature is reviewed.

Neuropathic pain following partial nerve injury in rats is suppressed by dietary soy.

Some humans with partial nerve injury present a syndrome of neuropathic sensory disorders which depend on the sympathetic activity (sympathetically-maintained pain, SMP). Several years ago we introduced a rat model for SMP, produced by tightly ligating 1/3-1/2 of the sciatic nerve, leading to a partial denervation of the hindpaw (Partial Sciatic Ligation, PSL model) [Seltzer, Z., Dubner, R. and Shir, Y., Pain, 43 (1990) 245-250]. After working with this model for several years we encountered difficulties in replicating it although rat strain, vendor, gender, age and weight, surgical approach and sensory testing procedures were not changed. We report here that this variability can be attributed, at least in part, to the diet the animals consumed. Rats fed perioperatively with soy-containing diets expressed significantly weaker neuropathic sensory disorders compared to rats fed on soy-free diets. We conclude that diet may greatly affect experimental outcome in the PSL model.

Oral methadone for the treatment of severe pain in hospitalized children: a report of five cases.

OBJECTIVE: Pain relief is still inadequate in many hospitalized patients, especially children in whom suboptimal use of analgesic drugs is still common. In the past 2 years, oral methadone has been used extensively in our institution for treating children with persistent pain from cancer, burns, or trauma who were capable of oral intake and whose pain was not relieved by nonopioid medications. SETTING: Tertiary university hospital. PATIENTS: Of the 70 children treated thus far with oral methadone, five are described in the present report. MAIN OUTCOME MEASURE: Pain relief, acceptability, and side effects of oral methadone in children with pain. RESULTS: Treatment with oral methadone (0.1% in 10% glucose, dose range of 0.2-0.6 mg/kg/day) for time periods of up to 6 weeks resulted in a rapid onset and stable pain relief, with no major side effects. No adverse responses were encountered after discontinuation of treatment. In three of the children, a parent-controlled analgesia regimen was successfully employed. CONCLUSIONS: Oral methadone can be recommended for babies and children who have severe pain that is not alleviated by nonopioid medications and who are capable of oral intake.

[Treating hospitalized children in severe pain with oral methadone].

Pain relief is usually inadequate in hospitalized patients, especially in children, either after surgery or with various medical conditions. Among other reasons, this is due to suboptimal use of available analgesic drugs. In the past 2 years oral methadone has become our opioid of choice for severe pain in hospitalized children who can take oral medication. More than 70 babies and children, aged 8 months to 9 years, who suffered mainly from pain due to burns or cancer, were treated by the in-hospital pain service. They received 0.1% methadone syrup, 0.2-0.4 mg/kg/day, for from a few days to more than a month. In most there was significant pain relief with no serious side-effects. In some, treatment could be changed to parent-controlled analgesia after a few days, with no adverse effects. We describe 5 of the children who present the advantages of oral methadone over other opioids.

[Intravenous lignocaine for chronic pain: an 18-month experience].

Intravenous injection of lignocaine relieves pain in animals with experimentally induced pain, and in man, mainly those with neuropathic pain. 106 patients were treated with intravenous lignocaine during a period of 18 months (212 treatment sessions). Blood pressure, heart rate and pain scores were continuously monitored after an intravenous bolus of lignocaine, 1 mg/kg, followed by continuous infusion of lignocaine, 5 mg/kg during 1 hour. There was significant pain relief after each session in most patients, lasting from a few hours to 4 weeks. There were no significant side effects. We present 2 of our patients. Due to its simplicity, efficacy and safety, intravenous lignocaine injection is recommended for those with neuropathic pain unrelieved by other therapeutic modalities.

Diet can modify autotomy behavior in rats following peripheral neurectomy.

Partial sciatic nerve ligation in rats (PSL) produces neuropathic pain disorders [Seltzer, Z., Dubner, R. and Shir, Y., Pain, 43 ( 1990) 205-18 (corrected) ]. Recently we reported that diet markedly affected the levels of these disorders. Here we questioned whether diet also affects neuropathic pain-related behavior in another model, produced by total denervation of the hindpaw following peripheral sciatic and saphenous neurectomy. Sabra rats and HA line rats were fed for 2-3 weeks preoperatively and up to 58 days postoperatively (PO) with one of five different diet formulas. We found that the autotomy behavior differed significantly between the diet groups. Surprisingly, in some diets the effects on autotomy and PSL models were different and even contrasting. Modulation of diet in humans may emerge as a novel therapy of neuropathic pain.

The effects of cardiac surgery on early and late pulmonary functions.

BACKGROUND: Impaired pulmonary functions are common in cardiac patients. Early and late effects of cardiac surgery on pulmonary function tests (PFTs) are presented. METHODS: Fifty patients undergoing cardiac surgery (coronary artery bypass grafting [CABG, 74%], valve replacement or valvuloplasty [20%] and combined procedures [6%]) were studied. Anginal and cardiac failure symptoms severity, and smoking history, were evaluated preoperatively. PFTs were studied and compared pre-, and 3 weeks and 3.5 months postoperatively. RESULTS: Pre- and postoperative PFTs were inversely related to severity of preoperative symptoms. Forced vital capacity (FVC) dropped from 98% of predicted preoperatively, to 63% (P < 0.00001) and 75% (P < 0.00001) 3 weeks and 3.5 months postoperatively, respectively. Expiratory volume in the first 1 s of forced expiration (FEV1.0) decreased from 95% to 61% (P < 0.00001) and 70% (P < 0.00001), respectively. Forced expiratory flow at 50% of vital capacity (FEF50) decreased from 85% to 56% (P < 0.00001) and 59% (P < 0.00001). Forced expiratory flow at 75% of vital capacity (FEF75) decreased from 77% to 47% and 47% (P < 0.00001). Peak expiratory flow rate (PEFR) declined from 101% to 66% (P < 0.00001) and 86% (P < 0.003). Maximal voluntary ventilation declined from 103% to 68% (P < 0.00001) and 77% (P < 0.00001). Only FVC (P < 0.0003), FEV1.0 (P < 0.02) and PEFR (P < 0.0001) partially recovered postoperatively. Smoking history did not affect perioperative PFTs. Pre-, but not postoperative FVC, FEV1.0, FEF50 and FEF75 were worse in valve than in CABG patients. CONCLUSIONS: Pulmonary functions deteriorate significantly for at least 3.5 months after cardiac surgery. Preoperative cardiac ischaemic and failure symptoms are inversely related to perioperative PFTs.

Cerebral protection using retrograde cerebral perfusion during hypothermic circulatory arrest.

BACKGROUND: Retrograde cerebral perfusion through the superior vena cava (SVC) has been proposed to protect the brain from ischaemic injury during profound hypothermic circulatory arrest (PHCA). Its contribution to cerebral protection is unclear. Furthermore, the addition of anaesthetic or vasodilating agents to the SVC perfusate to enhance brain protection, has never been described. METHODS: In three patients undergoing repair of the ascending aorta utilizing PHCA, the upper body was retrogradely perfused with cold (16 degrees C) blood through the SVC by the cardiopulmonary bypass pump. Electroencephalographic activity was monitored using a computerized electroencephalographic monitor (Cerebro Trac 2500, SRD). Perfusion pressure was measured at a port in the cannula connector. Etomidate or thiopentone was injected into the SVC perfusate to arrest reappearing electroencephalographic activity. Nitroglycerin or nitroprusside was injected into the perfusate to increase retrograde flow and maintain a constant perfusion pressure. RESULTS: During PHCA periods of up to 61 min, recurrent electroencephalographic activity was abolished by the retrograde administration of small boluses of etomidate (total 50 mg) or thiopentone (total 500 mg). Nitroprusside (100 micrograms) and nitroglycerin (2 micrograms.kg-1.min-1) increased retrograde flow from 220 to 550 and 660 ml.min-1, respectively, while maintaining perfusion pressure (25-26 mmHg). Recovery from anaesthesia and surgery was uneventful, with no adverse neurological sequelae. CONCLUSION: Injection of anaesthetic agents into the retrograde SVC perfusate during PHCA, can suppress reoccurring electroencephalographic activity and retrograde injection of vasodilators can facilitate an increase in perfusion. It is suggested that both may augment brain protection.