Pharmacological sympathetic denervation prevents the development of polycystic ovarian syndrome in rats injected with estradiol valerate.

BACKGROUND: The injection of estradiol valerate in female rats induces polycystic ovary syndrome, which is characterized by polycystic ovaries, anovulation, and hyperandrogenism. These characteristics have been associated with an increase in the ovarian concentration of norepinephrine, which occurs before establishing the polycystic ovary syndrome. The bilateral section of the superior ovarian nerve restores ovarian functions in animals with polycystic ovary syndrome. The superior ovarian nerve provides norepinephrine and vasoactive intestinal peptide to the ovary. An increase in the activity of both neurotransmitters has been associated with the development of polycystic ovary syndrome. The purpose of the present study was analyzed the participation of the noradrenergic nervous system in the development of polycystic ovary syndrome using guanethidine as a pharmacological tool that destroys peripheral noradrenergic nerve fibers. METHODS: Fourteen-day old female rats of the CIIZ-V strain were injected with estradiol valerate or vehicle solution. Rats were randomly allotted to one of three guanethidine treatment groups for denervation: 1) guanethidine treatment at age 7 to 27-days, 2) guanethidine treatment at age 14 to 34- days, and 3) guanethidine treatment at age 70 to 90- days. All animals were sacrificed when presenting vaginal oestrus at age 90 to 94-days. The parameters analyzed were the number of ova shed by ovulating animals, the ovulation rate (i.e., the numbers of ovulating animals/the numbers of used animals), the serum concentration of progesterone, testosterone, oestradiol and the immunoreactivity for tyrosine hydroxylase enzyme. All data were analyzed statistically. A p-value of less than 0.05 was considered significant. RESULTS: Our results show that the elimination of noradrenergic fibers before the establishment of polycystic ovary syndrome prevents two characteristics of the syndrome, blocking of ovulation and hyperandrogenism. We also found that in animals that have already developed polycystic ovary syndrome, sympathetic denervation restores ovulatory capacity, but it was not as efficient in reducing hyperandrogenism. CONCLUSION: The results of the present study suggest that the noradrenergic fibers play a stimulant role in the establishment of polycystic ovary syndrome.

Interventions for treating pain and disability in adults with complex regional pain syndrome.

BACKGROUND: There is currently no strong consensus regarding the optimal management of complex regional pain syndrome although a multitude of interventions have been described and are commonly used. OBJECTIVES: To summarise the evidence from Cochrane and non-Cochrane systematic reviews of the effectiveness of any therapeutic intervention used to reduce pain, disability or both in adults with complex regional pain syndrome (CRPS). METHODS: We identified Cochrane reviews and non-Cochrane reviews through a systematic search of the following databases: Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (DARE), Ovid MEDLINE, Ovid EMBASE, CINAHL, LILACS and PEDro. We included non-Cochrane systematic reviews where they contained evidence not covered by identified Cochrane reviews. The methodological quality of reviews was assessed using the AMSTAR tool.We extracted data for the primary outcomes pain, disability and adverse events, and the secondary outcomes of quality of life, emotional well being and participants' ratings of satisfaction or improvement. Only evidence arising from randomised controlled trials was considered. We used the GRADE system to assess the quality of evidence. MAIN RESULTS: We included six Cochrane reviews and 13 non-Cochrane systematic reviews. Cochrane reviews demonstrated better methodological quality than non-Cochrane reviews. Trials were typically small and the quality variable.There is moderate quality evidence that intravenous regional blockade with guanethidine is not effective in CRPS and that the procedure appears to be associated with the risk of significant adverse events.There is low quality evidence that bisphosphonates, calcitonin or a daily course of intravenous ketamine may be effective for pain when compared with placebo; graded motor imagery may be effective for pain and function when compared with usual care; and that mirror therapy may be effective for pain in post-stroke CRPS compared with a 'covered mirror' control. This evidence should be interpreted with caution. There is low quality evidence that local anaesthetic sympathetic blockade is not effective. Low quality evidence suggests that physiotherapy or occupational therapy are associated with small positive effects that are unlikely to be clinically important at one year follow up when compared with a social work passive attention control.For a wide range of other interventions, there is either no evidence or very low quality evidence available from which no conclusions should be drawn. AUTHORS' CONCLUSIONS: There is a critical lack of high quality evidence for the effectiveness of most therapies for CRPS. Until further larger trials are undertaken, formulating an evidence-based approach to managing CRPS will remain difficult.

Evidence-based interventional pain medicine according to clinical diagnoses. 16. Complex regional pain syndrome.

Complex regional pain syndrome (CRPS), formerly known as reflex sympathetic dystrophy is a pain syndrome with an unclear pathophysiology and unpredictable clinical course. The disease is often therapy resistant, the natural course not always favorable. The diagnosis of CRPS is based on signs and symptoms derived from medical history and physical examination. Pharmacological pain management and physical rehabilitation of limb function are the main pillars of therapy and should be started as early as possible. If, however, there is no improvement of limb function and persistent severe pain, interventional pain management techniques may be considered. Intravenous regional blocks with guanethidine did not prove superior to placebo but frequent side effects occurred.Therefore this technique receives a negative recommendation (2 A-). Sympathetic block is the interventional treatment of first choice and has a 2 B+ rating. Ganglion stellatum (stellate ganglion) block with repeated local anesthetic injections or by radiofrequency denervation after positive diagnostic block is documented in prospective and retrospective trials in patients suffering from upper limb CRPS. Lumbar sympathetic blocks can be performed with repeated local anesthetic injections. For a more prolonged lumbar sympathetic block radiofrequency treatment is preferred over phenol neurolysis because effects are comparable whereas the risk for side effects is lower (2 B+). For patients suffering from CRPS refractory to conventional treatment and sympathetic blocks, plexus brachialis block or continuous epidural infusion analgesia coupled with exercise therapy may be tried (2 C+). Spinal cord stimulation is recommended if other treatments fail to improve pain and dysfunction (2 B+). Alternatively peripheral nerve stimulation can be considered, preferentially in study conditions (2 C+).

Estudio descriptivo y prospectivo de 171 pacientes con distrofia simpático refleja en Aragón (España) / Clinical characteristics of reflex sympathetic dystrophy in Aragon (Spain). A prospective study of 171 patients

Hemos estudiado una población de 171 pacientes diagnosticados de distrofia simpático refleja (DSR). En esta población la DSR tiene, en gran medida, un origen secundario; siendo el traumatismo el más frecuente. El terreno predisponente más habitual es el psicológico. La DSR predomina en las extremidades inferiores. La mayor parte de las DSR han llegado en fase caliente. En general, la evolución ha sido satisfactoria con AINES, calcitonina y rehabilitación. En suma, nuestro estudio pone de manifiesto la gran heterogeneidad de este síndrome (AU)

We followed a total of 171 patients diagnosed with Reflex Sympathetic Dystrophy (RSD). This enigmatic condition normally has a secondary origin, being trauma the unleashing cause in most cases. Psychological predisposition plays a major role in developing the clinical state, which affects lower extremities more frequently. In this series, patients were first seen during the acute «warm» phase and the final outcome was generally good after a period of treatment with non-steroidal anti-inflammatory drugs (NSAID), calcitonin and physical therapy. However, a comprehensive review of the literature revealed the heterogeneity of this condition (AU)

Sympathetic nerves do not affect experimental ischemia-reperfusion injury of rat liver.

BACKGROUND: We investigated whether sympathetic, noradrenergic nerves participate in experimental acute ischemia-reperfusion injury of the rat liver. METHODS: Female Wistar rats (200-250 g body weight) were anesthetized with pentobarbital. After tracheotomy, we cannulated a carotid artery and jugular vein. The rats were divided in 2 groups (n = 8 per group). The control group received NaCl IV and the test group received the sympatholytic agent, guanethidine (3 mg/kg, IV). After 30 minutes of drug equilibration, laparotomy was performed to arrange the liver for temporary occlusion (by a ligature) of its vascular supply, corresponding with 70% reduction in hepatic blood flow. The rats were then allowed 60 minutes of equilibration. Thereafter, regional ischemia was induced for 30 minutes. The animals were then monitored for 2 hours of reperfusion. Blood samples for alanine aminotransferase (ALT) estimation (as a measure of injury to the parenchyma) were drawn immediately before ischemia, as well as 60 and 120 minutes after reperfusion. Readings of mean arterial pressure were taken during these times. RESULTS: After 2 hours of reperfusion, there were no significant differences between the groups with regard to ALT or mean arterial pressure. CONCLUSION: Sympathetic, noradrenergic nerves did not affect experimental ischemia-reperfusion injury of rat liver in the current model.

Computed tomography guided lumbar sympathetic block for complex regional pain syndrome in a child: a case report and review.

The aim of this paper is to describe the first reported use of computed tomography (CT) guided lumbar sympathetic block as treatment of a case of complex regional pain syndrome (CRPS) in a child. The potential aetiology of CRPS is discussed in relation to the mechanism of action of local anaesthetics used in the block. Based on the successful treatment of this child and the documented success of its use in adults, we conclude that despite the minimal dose of radiation given, CT guided lumbar sympathetic block is an important treatment option in CRPS in children.

Treatment of complex regional pain syndrome type I of the hand with a series of intravenous regional sympathetic blocks with guanethidine and lidocaine.

The aim of this study was to evaluate the efficacy of guanethidine and lidocaine in the treatment of complex regional pain syndrome (CRPS) type I of the hand. Seventeen patients, aged between 33 and 72 years, suffering from CRPS type I of the hand received two series of intravenous regional sympathetic block (Bier's block) sessions with guanethidine and lidocaine according to the following therapeutic protocol: (1) 5 sessions (once every second day) composed of intravenous regional administration of 15 mg guanethidine and 1 mg lidocaine/kg body weight each and (2) 20 sessions (twice a week) composed of intravenous regional administration of 10 mg guanethidine and 1 mg lidocaine/kg body weight each. Complete disappearance of pain and return of the normal function and movement of the extremity were achieved. No side effects were observed. The above-described therapeutic protocol method resulted in excellent pain relief and full restoration of both function and range of movement of the affected extremity in 17 patients suffering from CRPS type I of the hand.

Magnitude of abdominal incision affects the duration of postoperative ileus in rats.

BACKGROUND: The pathogenesis of reduced postoperative ileus (POI) in laparoscopic gastrointestinal (GI) surgery still remains controversial. The aim of this study was to investigate the effect of surgical incision on postoperative ileus. METHODS: The effects of length, depth, and site of the incision on GI transit were compared using the geometric center of 51Cr in rats. The inhibitory mechanism of abdominal incision on GI transit also was studied. RESULTS: The findings showed that 5 cm of abdominal skin and the 5-cm back muscle incision had no significant effect on GI transit. However, the 5-cm abdominal muscle-fascia incision and a 5-cm laparotomy significantly delayed GI transit. Gastrointestinal transit after a 5-cm laparotomy was significantly delayed, as compared with that of a 1-cm laparotomy regardless whether intestinal manipulation was performed or not. Guanethidine and yohimbine, but not propranolol, significantly improved the impaired GI transit after a 5-cm laparotomy. CONCLUSIONS: The results suggest that the longer and deeper abdominal incision more profoundly inhibits GI transit. The inhibitory effect of abdominal incision is mediated via the activation of the somatosympathetic reflex and alpha-2 adrenoceptors.

Treatment of reflex sympathetic dystrophy (CRPS type 1): a research synthesis of 21 randomized clinical trials.

A blinded meta analysis was performed on randomized clinical trials (RCT) on the medicinal treatment of reflex sympathetic dystrophy (complex regional pain syndrome type I) to assess the methodological quality and quantify the analgesic effect of treatments by calculating individual and summary effect sizes. The internal validity of 21 RCTs was investigated and the quality weighted summary effect size was calculated using a fixed effect model (Glass Delta). The methodological quality ranged from moderate to good (average 46%). Differences were found between the trials in inclusion/exclusion criteria, treatment methods, duration of treatments and trials, and measurement instruments. Statistical analysis was possible for four subgroups; one evaluating the analgesic effects of sympathetic suppressors in general (n = 12), one subgroup concerning the analgesic effects of guanethidine (n = 6), one investigating the analgesic effect of intravenous regional sympathetic blocks (n = 9), and one subgroup (n = 5) evaluating the analgesic effect of calcitonin. Except for the calcitonin subgroup (P = 0.002), the quality-weighted summary effect size of these subgroups were not significant. No significant analgesic effect by sympathetic suppressing agents could be established. Calcitonin seems to provide effective pain relief in reflex sympathetic dystrophy patients. The results of the present study show that weighting methodological quality influences the magnitude of the effect sizes of specific treatment methods. Future studies should control for methodological quality.

Sympathetically maintained pain.

Reflex sympathetic dystrophy (RSD) is a controversial condition, redefined in 1996 by an ad hoc International Association for the Study of Pain (IASP) task force. One of the strongest critiques against the entire concept of sympathetic-dependent pain is that patients labeled as having RSD harbor in reality a somatoform disorder. Here clinical cases are described to prove that other organic medical conditions may exist other than RSD and still present the clinical picture of pain, sensory, and vasomotor disorders and trophic changes. The analysis of each patient illustrates how the inappropriate diagnosis of RSD may lead to increased worsening of pain intensity, or delay the proper diagnosis, and consequently the appropriate treatment.

Effects of transvenous regional guanethidine block in the treatment of critical finger ischemia.

The objective of this study was to determine the effects of transvenous regional guanethidine block in the treatment of patients with critical finger ischemia. Twenty-seven patients (17 collagen vascular disease, four thromboangiitis obliterans, three embolism, three atherothrombosis) presenting with ischemic rest pain and/or ulcerations of the fingers received a single block with 5 mg guanethidine injected in 60 mL into the clinically more affected hand under 30 minutes of arterial arrest. Marked hyperemia was induced in the treated upper limb, increases (p < 0.01) in finger blood flow, finger skin temperature, and laser Doppler flux were higher and longer lasting than in forearm blood flow, persisting for a whole month. Effects in patients with ischemic finger ulcers were less pronounced than in those without, yet statistically significant increases of all evaluated parameters were observed in these patients too. No effects were seen in the contralateral untreated upper limb or in systemic blood pressure. Subjective symptoms (reduction of rest pain, numbness, vasospastic attacks) were improved in 25/27 (92.6%) patients, ischemic rest pain disappeared in 20/27 (74.1%), and complete healing of finger tip ulcerations within 1 month was achieved in 10/12 (83.3%) affected patients. No side effects were observed. This described method combines good clinical efficacy with lack of undesirable side effects and can be repeated easily. Therefore, this technique is recommended for broader clinical use.

Sympathetic nerve blocks in refractory sympathetic dystrophy syndrome.

The authors tried to evaluate the benefit of sympathetic nerve blocks with guanethidine in 32 patients with a sympathetic dystrophy syndrome who failed to respond to conventional treatment.

Intravenous guanethidine in patients with reflex sympathetic dystrophy.

BACKGROUND: Intravenous regional guanethidine Bier block (IVRGBB) has been used predominantly in Europe for treating reflex sympathetic dystrophy (RSD). Our experience in the United States, where its use has been limited, is reported. METHODS: Fifty-five patients received IVRGBB for RSD. Upper extremities received 20 mg (10 mg/ml) of guanethidine in 30-50 ml of 0.5% lidocaine; lower extremities received 40 mg in 40-75 ml of lidocaine (volume adjusted for size, weight, or prior adverse effect). Pain severity (mild, moderate, severe, excruciating) was obtained pretreatment. Pain severity and a global clinical assessment (GCA) (resolved, improved, no change, worse) were obtained following each treatment. The final GCA was analyzed vs: pretreatment score; age; sex; pain duration; number of treatments; and precipitating event. Adverse effects were documented. RESULTS: Of 55 enrolled patients, 2 were lost to follow-up, and 2 returned 1 and 4 years later for repeat treatment. Therefore, 53 patients were evaluated for 55 treatments. Age: 38.2 +/- 14.8 (SD) (range 10-77) years. Sex: 11 males, 44 females. Average pain duration: 2.0 +/- 1.7 years (3 days-7 years). Final assessment occurred at 3.88 +/- 5.21 months (6 days-22/3 years). Effect on pain: resolution-9.1%; improved-14.5%; no change-61.8%; worsening-14.5%. No significant relationship was found between GCA and the factors evaluated. There was a significant positive linear association between pretreatment pain and post treatment GCA (P = 0.032). Fifty-six adverse effects occurred in 19 (34.5%) patients (nausea, vomiting, orthostatic hypotension, dizziness, diarrhea, weakness). CONCLUSIONS: IVRGBB does not provide long-term pain relief and is associated with adverse effects in over 1/3 of patients.

Intra-articular guanethidine injection for resistant shoulder pain: a preliminary double blind study of a novel approach.

OBJECTIVE: To study the effect of intraarticular (IA) sympathetic blockade for the relief of resistant shoulder pain. METHODS: Eighteen patients with shoulder pain resistant to conventional treatment were allocated randomly to two groups, to receive either IA guanethidine 20 mg or IA saline. They were assessed for pain, and range of active movements, before injection and at one, four, and eight weeks after injection. RESULTS: There were no significant differences between groups, but the group receiving guanethidine showed greater improvement in pain relief at all three follow up visits compared with those receiving placebo (9% v 7% at one week; 15% v 6% at four weeks and 36% v 16% at eight weeks). The improvement reached significance (p < 0.05) at the eight week visit compared with baseline. The range of movement was not significantly improved in either group. CONCLUSION: The results suggest that IA guanethidine produced measurable improvement in resistant shoulder pain and that further studies of this novel approach are indicated.