Reducing the dose of neuromuscular blocking agents with adjuncts: a systematic review and meta-analysis.

BACKGROUND: Acute global shortages of neuromuscular blocking agents (NMBA) threaten to impact adversely on perioperative and critical care. The use of pharmacological adjuncts may reduce NMBA dose. However, the magnitude of any putative effects remains unclear. METHODS: We conducted a systematic review and meta-analysis of RCTs. We searched Medline, Embase, Web of Science, and Cochrane Database (1970-2020) for RCTs comparing use of pharmacological adjuncts for NMBAs. We excluded RCTs not reporting perioperative NMBA dose. The primary outcome was total NMBA dose used to achieve a clinically acceptable depth of neuromuscular block. We assessed the quality of evidence using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) criteria. Data are presented as the standardised mean difference (SMD); I2 indicates percentage of variance attributable to heterogeneity. RESULTS: From 3082 records, the full texts of 159 trials were retrieved. Thirty-one perioperative RCTs met the inclusion criteria for meta-analysis (n=1962). No studies were conducted in critically ill patients. Reduction in NMBA dose was associated with use of magnesium (SMD: -1.10 [-1.44 to -0.76], P<0.001; I2=85%; GRADE=moderate), dexmedetomidine (SMD: -0.89 [-1.55 to -0.22]; P=0.009; I2=87%; GRADE=low), and clonidine (SMD: -0.67 [-1.13 to -0.22]; P=0.004; I2=0%; GRADE=low) but not lidocaine (SMD: -0.46 [-1.01 to -0.09]; P=0.10; I2=68%; GRADE=moderate). Meta-analyses for nicardipine, diltiazem, and dexamethasone were not possible owing to the low numbers of studies. We estimated that 30-50 mg kg-1 magnesium preoperatively (8-15 mg kg h-1 intraoperatively) reduces rocuronium dose by 25.5% (inter-quartile range, 14.7-31). CONCLUSIONS: Magnesium, dexmedetomidine, and clonidine may confer a clinically relevant sparing effect on the required dose of neuromuscular block ing drugs in the perioperative setting. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42020183969.

Abstinence and reduced frequency of use are associated with improvements in quality of life among treatment-seekers with cannabis use disorder.

BACKGROUND AND OBJECTIVE: Many patients with cannabis use disorder (CUD) do not achieve or do not have abstinence as a goal of treatment, rather they reduce their use. Assessing outcome measures as they relate to functioning and reductions in cannabis use is an important area of study. Quality of life (QoL) shows promise as one such measure. Past studies have demonstrated gender differences in QoL and CUD. We aim to assess (1) the relationship between cannabis use and QoL and (2) gender effects in an outpatient medication treatment study for CUD. METHODS: Data from an 11-weeks, double-blind, placebo-controlled trial of lofexidine and dronabinol for CUD (n = 62) was analyzed. Pearson's correlations between baseline QoL as measured with the Quality of Life, Enjoyment, and Satisfaction Questionnaire-Short Form (QLES-Q-SF) and cannabis use assessed with modified timeline follow-back (TLFB) were examined. Multiple linear regression models of cannabis use on end of study QLES-Q-SF were analyzed, while adjusting for baseline QLES-Q-SF, study arm, and gender. Moderation effects with gender were also tested. RESULTS: No significant association between baseline cannabis use and QoL was found. End of study abstinence (F1,47 = 8.34, p = .006) and reduced proportion of using days (F1,47 = 9.48, p = .004) were each significantly associated with end of study QoL. Reduction in grams (F1,27 = 0.25, p = .62) was not associated with QoL at end of study. Gender was not a significant moderator. DISCUSSION AND CONCLUSIONS: Abstinence and lower frequency of use are associated with higher QoL, regardless of gender. SCIENTIFIC SIGNIFICANCE: This is the first time QoL has been demonstrated to change over the course of CUD medication treatment. QoL is an important outcome in CUD treatment. TRIAL REGISTRATION: NCT01020019. (Am J Addict 2018;27:101-107).

Effect of clonidine on the efficacy of lignocaine local anesthesia in dentistry: A systematic review and meta-analysis of randomized, controlled trials.

Alternatives to adrenaline with lignocaine local anesthesia, such as clonidine, have been trialed in various randomized, controlled trials. Therefore, the aim of the present systematic review was to compile the available evidence on using clonidine with lignocaine for dental anesthesia. Electronic databases were searched for eligible studies. A data-extraction form was created, extracted data were analyzed using non-Cochrane mode in RevMan 5.3 software. Heterogeneity between the studies were assessed using the forest plot, I2 statistics (where >50% was considered to have moderate-to-severe heterogeneity), and χ2 -test. Random-effects models were used because of moderate heterogeneity. Five studies were included for the final review. While clonidine was found to significantly shorten the onset of local anesthesia when measured subjectively, no significant difference was observed objectively. No significant difference was observed in the duration and postoperative analgesia. Stable hemodynamic parameters within the safe range were observed postoperatively when clonidine was used. Clonidine could be considered as an alternative to adrenaline in cases of contraindications to adrenaline, such as like cardiac abnormalities, hypertension, and diabetes.

Multimodal therapeutic approach of vaginismus: an innovative approach through trigger point infiltration and pulsed radiofrequency of the pudendal nerve / Terapêutica multimodal do vaginismo: abordagem inovadora por meio de infiltração de pontos gatilho e radiofrequência pulsada do nervo pudendo

Abstract Vaginismus is a poorly understood disorder, characterized by an involuntary muscular spasm of the pelvic floor muscles and outer third of the vagina during intercourse attempt, which results in aversion to penetration. It is reported to affect 1-7% of women worldwide. With this report the authors aim to describe the case of a young patient with vaginismus in whom techniques usually from the chronic pain domain were used as part of her multimodal therapeutic regimen.

Resumo O vaginismo é uma doença pouco compreendida que se caracteriza por uma contração muscular involuntária dos músculos do pavimento pélvico e do terço externo da vagina durante as tentativas de intercurso sexual, o que resulta em aversão à penetração. Estima-se que possa afetar entre 1%-7% da população feminina mundial. Com este relato os autores pretendem apresentar o caso de uma paciente jovem com vaginismo na qual foram usadas técnicas habitualmente do domínio da medicina da dor crônica como parte do seu esquema terapêutico multimodal.

[Multimodal therapeutic approach of vaginismus: an innovative approach through trigger point infiltration and pulsed radiofrequency of the pudendal nerve]. / Terapêutica multimodal do vaginismo: abordagem inovadora por meio de infiltração de pontos gatilho e radiofrequência pulsada do nervo pudendo.

Vaginismus is a poorly understood disorder, characterized by an involuntary muscular spasm of the pelvic floor muscles and outer third of the vagina during intercourse attempt, which results in aversion to penetration. It is reported to affect 1-7% of women worldwide. With this report the authors aim to describe the case of a young patient with vaginismus in whom techniques usually from the chronic pain domain were used as part of her multimodal therapeutic regimen.

The effect of serratus plane block performed under direct vision on postoperative pain in breast surgery.

STUDY OBJECTIVES: To determine the effectiveness of serratus plane block performed under direct vision on postoperative pain after mastectomy. DESIGN: We performed a retrospective study of elective breast surgery patients undergoing mastectomy over 6 months. We collected data on the outcomes for the pain score and use of analgesia in recovery, the use of analgesia and antiemetics overnight, and the pain score and mobilization status of the patient 1 day after the operation. SETTING: Breast cancer is the most common cancer in women, and mastectomy is commonly performed as part of the management. A mastectomy can cause significant acute pain which progresses to chronic pain in 25% to 60% of women. Recent studies have suggested that a serratus plane block is a viable alternative to regional anesthetic techniques without the side effect profile and that injection of local anesthetic into serratus anterior provided predictable and effective anesthesia to the chest wall. Serratus blocks target the thoracic nerves more selectively than pectoral blocks, and local blocks can reduce the use of opiates postoperatively thereby lessening opiate-related side effects. PATIENTS: Our sample included 16 patients who had received a serratus block and 11 patients who only had wound infiltration with levobupivacaine with adrenaline and clonidine. INTERVENTION: Serratus plane block was conducted by injecting 50% of the totally available levobupivacaine 0.375% with adrenaline and clonidine deep to serratus anterior under direct observation. MAIN RESULTS: No patients receiving a serratus block suffered severe pain in recovery or day 1 postoperatively. Patients receiving wound infiltration alone had 2 patients suffering severe pain in recovery and 3 patients suffering severe pain day 1 postoperatively. CONCLUSION: Serratus block provides effective regional anesthesia, suitable for mastectomies, and currently appears to be superior to wound infiltration alone. However, further data will need to be collected to support this finding.

Compounded Topical Analgesics for Chronic Pain.

Analgesic medications compounded for topical use are gaining popularity for the management of chronic pain. The advantages of topical pain medications include reduction of systemic adverse effects, improved patient acceptance, few drug interactions, ease of dose determination, avoidance of first-pass metabolism, and direct access to the target site. Compounded topical medications typically use a mixture of 3 or more single medications to achieve multiple complementary effects at lower doses of each individual medication. Herein, we review the mechanisms, adverse effects, and evidence for some of the most commonly used medications in topical compounds for pain management. Because more topical medications are used for chronic pain, dermatologists can expect an increase in irritant and allergic contact dermatitis related to these medications.

Comparison of pulpal anesthesia and cardiovascular parameters with lidocaine with epinephrine and lidocaine with clonidine after maxillary infiltration in type 2 diabetic volunteers.

OBJECTIVES: The pulpal anesthetic and cardiovascular parameters obtained by 2 % lidocaine with epinephrine (LE; 1:80,000) or clonidine (LC; 15 mcg/ml) were studied in diabetes mellitus (DM) type 2 and healthy volunteers (72), after maxillary infiltration anesthesia. MATERIALS AND METHODS: Onset and duration of pulpal anesthesia were measured by electric pulp tester; vasoconstrictive effect of used local anesthetic mixtures by laser Doppler flowmetry (LDF) through pulpal blood flow (PBF); systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were registered by electrocardiogram monitoring. RESULTS: Onset of pulpal anesthesia was shorter for LC than for LE in healthy, while it was not different in diabetic participants; duration of pulpal anesthesia was significantly longer in type 2 diabetic participants, regardless of used anesthetic mixture. Significant reduction of PBF with LE was observed during 45 min in healthy and 60 min in diabetic participants, while with LC such reduction was observed during 45 min in both groups. LE caused a significant increase of SBP in the 5th and 15th minutes in diabetic versus healthy participants, while LC decreased SBP from the 10th to 60th minutes in healthy versus diabetic participants. CONCLUSIONS: DM type 2 influences duration of maxillary infiltration anesthesia obtained with LE and LC, and systolic blood pressure during LE anesthesia. CLINICAL RELEVANCE: The obtained results provide elements for future protocols concerning intraoral local anesthesia in DM type 2 patients.

Evaluation of the Percutaneous Absorption of Ketamine HCl, Gabapentin, Clonidine HCl, and Baclofen, in Compounded Transdermal Pain Formulations, Using the Franz Finite Dose Model.

OBJECTIVE: This study evaluates the ability of four commonly used analgesics (ketamine HCl, gabapentin, clonidine HCl, and baclofen), when incorporated into two transdermal compounding bases, Lipoderm and Lipoderm ActiveMax, to penetrate human cadaver trunk skin in vitro, using the Franz finite dose model. DESIGN: In vitro experimental study. Methods. Ketamine HCl 5% w/w, gabapentin 10% w/w, clonidine HCl 0.2% w/w, and baclofen 2% w/w were compounded into two transdermal bases, Lipoderm and Lipoderm ActiveMax. Each compounded drug formulation was tested on skin from three different donors and three replicate skin sections per donor. The Franz finite dose model was used in this study to evaluate the percutaneous absorption and distribution of drugs within each formulation. RESULTS: Rapid penetration to peak flux was detected for gabapentin and baclofen at approximately 1 hour after application. Clonidine HCl also had a rapid penetration to peak flux occurring approximately 1 hour after application and had a secondary peak at approximately 40 hours. Ketamine HCl exhibited higher overall absorption rates than the other drugs, and peaked at 6­10 hours. Similar patterns of drug distribution within the skin were also observed using both transdermal bases. CONCLUSIONS: This study suggests that the combination of these 4 analgesic drugs can be successfully delivered transdermally, using either Lipoderm or Lipoderm ActiveMax. Compounded transdermal drug preparations may then provide physicians with an alternative to traditional oral pain management regimens that can be personalized to the specific patient with the potential for enhanced pain control.

Topical treatment in pain medicine: from ancient remedies to modern usage.

Over several millennia, substances have been applied to the skin for treatment of pain. Some ingredients are in current use; others have been discontinued. Mechanisms of action include interactions with nociceptive neural networks and inflammatory processes. Substances must penetrate the stratum corneum barrier and vehicles that enhance penetration have been developed. Topical drugs with links to the past include menthol, capsaicin, some opioids, local anesthetic agents and NSAIDs. Mandragora is also described as an example of a herbal remedy that has been discontinued due to its toxicity. The future for topical drugs is promising, with the advent of new drugs tailored for specific pain mechanisms and the development of both penetration enhancers and sterile preparation methods.

Development of an LC-MS/MS method for determining the pharmacokinetics of clonidine following oral administration of Zhenju antihypertensive compound.

Zhenju antihypertensive compound (ZJAHC) is a combined Chinese-Western medicine formula including clonidine (CLO), hydrochlorothiazide (HCT), rutin, Chrysanthemum indicum extract and pearl powder. Compared with CLO preparations, ZJAHC shows improved activities and decreased adverse effects. It is believed that the side effects of CLO are caused by its high peak plasma concentration. Hence, study of the influence of ZJAHC on the pharmacokinetic behaviors of clonidine seems essential. In present study, the plasma concentrations of CLO were determined with a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The MS/MS transitions monitored for clonidine and internal standard were 230.2 → 213.1 and 152.2 → 110.2, respectively. The analyte was quantified in a single run within 3 min. The pharmacokinetic study showed that the area under the plasma concentration-time curve of CLO in ZJAHC (60 µg/kg CLO) was similar to that of CLO-HCT-high (120 µg/kg CLO) but the peak concentration was much lower than that in CLO-HCT-high. ZJAHC could enhance the bioavailability without greatly increasing peak concentration of clonidine. This comprehensive effect of enhancing the bioavailability and avoiding the high peak plasma concentration for CLO might mainly result from the co-contribution of Western medicine and traditional Chinese medicine (TCM), while the effect of TCM was stronger than that of Western medicine.

[Clinical and physiological rationale for use of clonidine with articaine and adrenaline for local anesthesia in pediatric dentistry].

The study evaluated the effect of local anesthesia with articaine in different combinations with epinephrine and clonidine (articaine (4%) + epinephrine (1:200 000), articaine (4%) + clonidine (1:100 000), articaine (4%) + epinephrine (1:200 000) + clonidine (1:100 000), articaine (4%) + epinephrine (1:400 000) + clonidine (1:100 000)), on a number of physiological parameters in pediatric dental practice that characterize cardiovascular system, patient's degree of adaptation to a stressful situation and efficacy of analgesia. It is shown that in terms of impact on the cardiovascular system and stress adaptation indicators anesthesia including combination of epinephrine (1: 200 000) and clonidine (1: 100 000) in the anesthetic solution is the safest. Furthermore, this method ensures the most appropriate analgesic effect.

[Efficiency of teeth local anesthesia by articaine-containing formulation with adrenaline and clonidine in pediatric dentistry].

The study evaluated duration and depth of the local infiltration anesthesia by articaine with different combinations of epinephrine and clonidine : articaine (4%) + epinephrine (1: 200 000), articaine (4%) + clonidine (1:100 000), articaine (4%) + epinephrine (1:200 000) + clonidine (1:100 000), articaine (4%) + epinephrine (1: 400 000) + clonidine (1:100, 000) in pediatric dental practice. It was revealed that the replacement of the vasoconstrictor epinephrine on clonidine associated with reduced depth and duration of analgesia. This increased efficiency is provided by inclusion of epinephrine (1:200 000), and clonidine (1:100 000) into anesthetic solution, which provided statistically significant increase in depth and duration of anesthesia.

Transdermal clonidine in the treatment of severe hyperemesis. A pilot randomised control trial: CLONEMESI.

OBJECTIVE: To study the efficacy of transdermal clonidine in the treatment of severe refractory hyperemesis gravidarum (HG), the most severe illness of pregnancy. DESIGN: The study had a randomised, double -blind, placebo-controlled, cross-over design (RCT). SETTING: Single tertiary referral hospital after admission of patients. SAMPLE: Twelve women of gestational age 6-12 weeks and a major grade of HG clinical severity who were unresponsive to standard antiemetic treatment. METHODS: The patients were randomly treated with and without the active drug (5 mg patch) for two consecutive periods of 5 days. The patients were allocated to a random list to receive first placebo and then active drug or the other way round. Other antiemetic drugs were administered on a scheduled or as-needed basis. All patients received intravenous hydration and thiamine supplementation. MAIN OUTCOME MEASURES: Pregnancy Unique Quantification of Emesis (PUQE) and visual analog scale (VAS) clinical scores, positive morning urine ketonuria, number of doses of standard antiemetic drugs required, and number of days off intravenous therapy were compared in the two periods. RESULTS: Transdermal clonidine led to a significantly greater improvement compared with placebo of the primary (PUQE score P = 0.026 CI 0.43-3.24; VAS score P = 0.010 CI 2.17-12.83) and secondary outcome measures. A reduction of blood pressure was reported for systolic 6 mmHg P = 0.01 and diastolic 3 mmHg P = 0.055. CONCLUSIONS: This preliminary RCT demonstrates the efficacy of transdermal clonidine in the treatment of severe HG, leading to a significant reduction of symptoms and reducing the need for other supportive measures and medications.

α(2) noradrenergic receptor suppressed CaMKII signaling in spinal dorsal horn of mice with inflammatory pain.

Intrathecal application of α2 noradrenergic receptor agonists effectively alleviates the pathological pain induced by peripheral tissue injury. However, the spinal antinociceptive mechanisms of α2 noradrenergic receptors remain to be characterized. The present study performed immunohistochemistry and western blot to elucidate the signaling pathway initiated by α2 noradrenergic receptors in spinal dorsal horn of mice, and identified calcium/calmodulin-dependent protein kinase II (CaMKII) as an important target for noradrenergic suppression of inflammatory pain. Our data showed that intraplantar injection of Complete Freund's Adjuvant (CFA) substantially enhanced CaMKII autophosphorylation at Threonine 286, which could be abolished by intrathecal administration of α2 noradrenergic receptor agonist clonidine. Gi protein-coupled α2 noradrenergic receptor might inhibit cAMP-dependent protein kinase (PKA) to disturb CaMKII signaling. We found that pharmacological activation of PKA in intact mice also enhanced spinal CaMKII autophosphorylation level, which was completely antagonized by clonidine. Moreover, direct PKA inhibition in CFA-injected mice mimicked the suppressive effect of α2 noradrenergic receptors on CaMKII. PKA inhibition has been shown to downregulate CaMKII by enhancing protein phosphatase activity. Consistent with this notion, spinal treatment with protein phosphatase inhibitor okadaic acid ruled out clonidine-mediated CaMKII dephosphorylation in CFA-injected mice. Through PKA/protein phosphatase/CaMKII pathway, clonidine noticeably decreased CFA-evoked phosphorylation of N-methyl-d-aspartate subtype glutamate receptor GluN1 and GluN2B subunit as well as α-amino-3-hydroxy-5-methylisoxazole-4-propionic Acid subtype glutamate receptor GluA1 subunit. These data suggested that interference with CaMKII signaling might represent an important mechanism underlying noradrenergic suppression of inflammatory pain.

Status dystonicus: a practice guide.

Status dystonicus is a rare, but life-threatening movement disorder emergency. Urgent assessment is required and management is tailored to patient characteristics and complications. The use of dystonia action plans and early recognition of worsening dystonia may potentially facilitate intervention or prevent progression to status dystonicus. However, for established status dystonicus, rapidly deployed temporizing measures and different depths of sedation in an intensive care unit or high dependency unit are the most immediate and effective modalities for abating life-threatening spasms, while dystonia-specific treatment takes effect. If refractory status dystonicus persists despite orally active anti-dystonia drugs and unsuccessful weaning from sedative or anaesthetic agents, early consideration of intrathecal baclofen or deep brain stimulation is required. During status dystonicus, precise documentation of dystonia sites and severity as well as the baseline clinical state, using rating scales and videos is recommended. Further published descriptions of the clinical nature, timing of evolution, resolution, and epidemiology of status dystonicus are essential for a better collective understanding of this poorly understood heterogeneous emergency. In this review, we provide an overview of the clinical presentation and suggest a management approach for status dystonicus.

Effect of clonidine added to lidocaine for sub-Tenon's (episcleral) anesthesia in cataract surgery.

PURPOSE: We aimed to evaluate the duration of anesthesia, analgesia and ocular akinesia of clonidine added to lidocaine in sub-Tenon's anesthesia in patients undergoing cataract surgery. METHODS: Forty patients were prospectively enrolled. They were randomized to two sub-Tenon's anesthesia groups: group L (6 ml of lidocaine 2 %, 1 ml of 0.9 % saline and 25 UI/ml of hyaluronidase), and group C (6 ml lidocaine 2 %, clonidine 1 µg/kg, 1 ml of 0.9 % saline and 25 UI/ml of hyaluronidase). Duration of sensory anesthesia, ocular akinesia in all directions, akinesia of the levator palpebrae superioris and orbicularis oculi muscles, the duration of analgesia (time to the first postoperative use of analgesics), the overall use of analgesics and the presence of adverse effects were recorded . RESULTS: The duration of sensory anesthesia and akinesia of the four rectus, levator palpebrae superioris, and orbicularis oculi muscles was significantly longer in group C (p < 0.05). The number of patients who required analgesics was similar between the groups but the duration of analgesia was longer in group C (p < 0.05). No significant adverse effects were observed. CONCLUSION: The addition of clonidine 1 µg/kg to 2 % lidocaine in sub-Tenon's anesthesia for cataract surgery increased the duration of sensory anesthesia, ocular akinesia, and the duration of analgesia.

Characterization and optimization of GMO-based gels with long term release for intraarticular administration.

Osteoarthritis is characterized by slow degenerative processes in the articular cartilage within synovial joints. It could be interesting to develop a sustained-release formulation that could be effective on both pain/inflammation and restoration of mechanical integrity of the joint. Recently, an injectable system based on glycerol monooleate (GMO), containing clonidine as a model hydrophilic analgesic/anti-inflammatory drug and hyaluronic acid as a viscoelastic scaffold, showed promising potential as a biodegradable and biocompatible preparation to sustain the drug activity. However, drug release from the system is relatively fast (complete within 1 week) and the underlying drug release mechanisms not fully understood. The aims of this study were: (i) to significantly improve this type of local controlled drug delivery system by further sustaining clonidine release, and (ii) to elucidate the underlying mass transport mechanisms. The addition of FDA-approved inactive ingredients such as sodium oleate or purified soybean oil was found to be highly effective. The release rate could be substantially reduced (e.g., 50% release after 10 days), due to the increased hydrophobicity of the systems, resulting in slower and reduced water uptake and reduced drug mobility. Interestingly, Fick's second law of diffusion could be used to quantitatively describe drug release.

Effect of adding cervical facet joint injections in a multimodal treatment program for long-standing cervical myofascial pain syndrome with referral pain patterns of cervical facet joint syndrome.

PURPOSE: Cervical facet joint (CFJ) syndrome is a common disorder observed in chronic pain of the cervical region, especially in long-standing myofascial pain syndrome (MPS). This study aimed to investigate the effects of therapeutic CFJ injections on patients with long-standing cervical MPS with referral pain patterns of CFJ syndrome. METHODS: Four hundred patients presented with long-standing cervical MPS with referral pain patterns of CFJ syndrome over a period of 6 months. A randomized clinical trial was performed wherein 200 patients (group 1) received therapeutic CFJ injections at bilateral C5/C6 and C6/C7 after diagnostic, controlled double-blind blocks. The same cointerventions, such as medication and a home exercise program, were simultaneously applied to patients in group 1 and the noninjection group (group N). Cervical range of motion (CROM), mean reduction of numeric rate scale (NRS) for pain, and comorbid tension-type headache were compared between groups during the 1-year follow-up period. Treatment duration and symptom-free periods were compared according to age group. RESULTS: Group 1 showed increased CROM, increased mean NRS pain reduction, and decreased incidence of combined tension-type headache compared with group N during the follow-up. Younger patients in group 1 required a shorter treatment cycle and experienced a longer symptom-free period. CONCLUSION: Addition of therapeutic CFJ injections to a multimodal treatment program is a useful therapeutic modality for patients, especially young patients, suffering from long-standing MPS with referral pain of CFJ syndrome.

Effect of magnesium chloride on psychomotor activity, emotional status, and acute behavioural responses to clonidine, d-amphetamine, arecoline, nicotine, apomorphine, and L-5-hydroxytryptophan.

BACKGROUND: The beneficial effects of magnesium (Mg) salts on central manifestations of Mg deficiency are well known. Mg replacement therapy can be effective to prevent some of the serious depression-like and anxiety-related behaviour sequelae of Mg deficiency. However, few experimental studies have been undertaken on Mg-deficiency-induced behavioural changes. Even fewer studies have been carried out on acute behavioural responses to clonidine, D-amphetamine, arecoline, nicotine, apomorphine, and L-5-hydroxytryptophan (HTP), which might characterize possible neuromediator changes in Mg deficiency. The effects of correcting Mg deficiency by magnesium chloride (MgCl2 · 6H2O) and the combination of this salt with vitamin B6, on the behavioural manifestations of Mg deficiency have never been described as well. OBJECTIVE: The aims of this study were: to estimate effect of MgCl2 · 6H2O alone and in combination with vitamin B6 on acute behavioural responses to agonists or blockers of the main neurotransmitter systems in CNS, psychomotor activity and emotional status of rats fed with Mg-deficient diet for 49 days. In our study open field test has shown that in Mg-deficient rats locomotor activity and vertical activity, number of visiting and residence time in central squares were decreased significantly. In the elevated plus maze test, the number of visiting open arms and residence time of rats were significantly less as compared with the control group. In the forced swimming test, time immobile was significantly increased by 44.29% and time of swimming was decreased by 52.79% compared to control. RESULTS: In our study Mg-deficient rats were more sensitive to d-amphetamine-induced motor stereotypes. Mg deficiency antagonized 5-hydroxytryptophan-induced head-twitch response and arecoline-induced tremor. Supplement of MgCl2 · 6H2O with vitamin B6 administered to a Mg-deficient rat increased the Mg level in plasma and erythrocytes. Furthermore, this increase was in relation to vitamin B6 given to the animal. Mg supplementation alone and in combination with pyridoxine normalized acute behavioural responses to d-amphetamine, 5-hydroxytryptophan, and arecoline in Mg deficient rats with a return to pre-deficient levels observed in the Mg sufficient group. DISCUSSION: Combination of Mg salts and pyridoxine hydrochloride can be effective at treating some behavior form of primary Mg deficiency.