Relief Strategies Research Articles

α2 Adrenoceptor: a Target for Neuropathic Pain Treatment.

Neuropathic pain is originated from different alterations of the nervous system. The difficulty of treatment strongly impairs quality of life of affected people. It is associated with severe, chronic sensory disturbances characterized by spontaneous pain, increased responsiveness to painful stimuli and pain perceived in response to normally non-noxious stimuli. The underlying mechanisms are complex and involve both peripheral and central nervous components. The noradrenergic system plays a pivotal role in the control of pain since its widespread distribution in the "pain matrix" representing a valuable therapeutic target. This review focused on the α2 adrenoceptor subtype modulation as strategy for neuropathic pain relief. Drugs acting as direct α2 adrenoceptor agonists (clonidine and dexmedetomidine) were analyzed as well as the indirect α2 adrenoceptor modulators. The overview included norepinephrine reuptake inhibitors (reboxetine, maprotiline), serotonin/norepinephrine reuptake inhibitors (venlafaxine, milnacipran, amitriptyline, duloxetine, bicifadine) and the compounds characterized by a double pharmacodynamic mechanism combining the norepinephrine reuptake inhibition and the μ opioid agonist profile (tramadol and tapentadol). A summary of recent compounds was illustrated.

A Model Practice Template for Hydrotherapy in Labor and Birth.

A Model Practice Template for Hydrotherapy in Labor and Birth.

Intravascular and hybrid intraoperative stent placement for baffle obstruction in transposition of the great arteries after atrial switch.

To report our experience with intravascular and hybrid intra-operative stent placement for baffle obstruction in patients with complete transposition of the great arteries (TGA) after the atrial switch (Mustard/Senning) operation. Venous baffle obstruction is a challenging complication after atrial switch operation in patients with TGA. Traditional treatment options include intravascular stenting or surgery. A retrospective analysis of Mayo Clinic's electronic medical record was completed to identify consecutive pediatric and adult patients with TGA after atrial switch who underwent baffle stent implantation from 1994 to 2015. Overall, 64 patients were referred for cardiac catheterization, in whom 47 (73%) were noted to have hemodynamic and angiographic evidence of baffle obstruction. A total of 20 patients mean age 33 (range: 8-46) years old underwent stent implantation of baffle stenosis at a mean of 33 (range: 7.5-45) years after initial atrial switch operation (Mustard, n = 19; Senning, n = 1). Overall, 27 baffles were stented in 20 patients via the following approaches: intravascular (17); hybrid surgical (3); staged intravascular & hybrid (2). Sites of stent placement were: superior vena cava (SVC) (13); inferior vena cava (IVC) (9); pulmonary venous baffle (5). Three patients had stent placement in the SVC and IVC baffles during the same procedure. Procedural adverse events occurred in 2/22 cases (9%) including creation of unintentional baffle leak (n = 1) and stent migration (n = 1). There was no procedure-related mortality. At follow-up (median 2, range 0.02-10 years), significantly improved NYHA class and mean Doppler baffle gradient were demonstrated (P < 0.05). Mild baffle re-stenosis (mean Doppler gradient; 2-3 mmHg) occurred in two patients who have not required re-intervention. Trivial baffle leak was noted in four patients. Baffle re-intervention was only occurred in one patient. One patient with pre-procedural Class IV symptoms died 3.5 months after stent implantation. This study is the largest reported experience of intravascular and intra-operative hybrid stent placement for patients with TGA after atrial switch. Transcatheter and minimally invasive hybrid intraoperative surgical stent placement are an effective strategy for relief of systemic and pulmonary venous baffle obstruction. © 2016 Wiley Periodicals, Inc.

Spinal Fbxo3-Dependent Fbxl2 Ubiquitination of Active Zone Protein RIM1α Mediates Neuropathic Allodynia through CaV2.2 Activation.

Spinal plasticity, a key process mediating neuropathic pain development, requires ubiquitination-dependent protein turnover. Presynaptic active zone proteins have a crucial role in regulating vesicle exocytosis, which is essential for synaptic plasticity. Nevertheless, the mechanism for ubiquitination-regulated turnover of presynaptic active zone proteins in the progression of spinal plasticity-associated neuropathic pain remains unclear. Here, after research involving Sprague Dawley rats, we reported that spinal nerve ligation (SNL), in addition to causing allodynia, enhances the Rab3-interactive molecule-1α (RIM1α), a major active zone protein presumed to regulate neural plasticity, specifically in the synaptic plasma membranes (SPMs) of the ipsilateral dorsal horn. Spinal RIM1α-associated allodynia was mediated by Fbxo3, which abates Fbxl2-dependent RIM1α ubiquitination. Subsequently, following deubiquitination, enhanced RIM1α directly binds to CaV2.2, resulting in increased CaV2.2 expression in the SPMs of the dorsal horn. While exhibiting no effect on Fbxo3/Fbxl2 signaling, the focal knockdown of spinal RIM1α expression reversed the SNL-induced allodynia and increased spontaneous EPSC (sEPSC) frequency by suppressing RIM1α-facilitated CaV2.2 expression in the dorsal horn. Intrathecal applications of BC-1215 (a Fbxo3 activity inhibitor), Fbxl2 mRNA-targeting small-interfering RNA, and ω-conotoxin GVIA (a CaV2.2 blocker) attenuated RIM1α upregulation, enhanced RIM1α expression, and exhibited no effect on RIM1α expression, respectively. These results confirm the prediction that spinal presynaptic Fbxo3-dependent Fbxl2 ubiquitination promotes the subsequent RIM1α/CaV2.2 cascade in SNL-induced neuropathic pain. Our findings identify a role of the presynaptic active zone protein in pain-associated plasticity. That is, RIM1α-facilitated CaV2.2 expression plays a role in the downstream signaling of Fbxo3-dependent Fbxl2 ubiquitination/degradation to promote spinal plasticity underlying the progression of nociceptive hypersensitivity following neuropathic injury. Ubiquitination is a well known process required for protein degradation. Studies investigating pain pathology have demonstrated that ubiquitination contributes to chronic pain by regulating the turnover of synaptic proteins. Here, we found that the spinal presynaptic active zone protein Rab3-interactive molecule-1α (RIM1α) participates in neuropathic pain development by binding to and upregulating the expression of CaV2.2. In addition, Fbxo3 modifies this pathway by inhibiting Fbxl2-mediated RIM1α ubiquitination, suggesting that presynaptic protein ubiquitination makes a crucial contribution to the development of neuropathic pain. Research in this area, now in its infancy, could potentially provide a novel therapeutic strategy for pain relief.

Pain and pain management in haemophilia.

Joint pain is common in haemophilia and may be acute or chronic. Effective pain management in haemophilia is essential to reduce the burden that pain imposes on patients. However, the choice of appropriate pain-relieving measures is challenging, as there is a complex interplay of factors affecting pain perception. This can manifest as differences in patients’ experiences and response to pain, which require an individualized approach to pain management. Prophylaxis with factor replacement reduces the likelihood of bleeds and bleed-related pain, whereas on-demand therapy ensures rapid bleed resolution and pain relief. Although use of replacement or bypassing therapy is often the first intervention for pain, additional pain relief strategies may be required. There is an array of analgesic options, but consideration should be paid to the adverse effects of each class. Nevertheless, a combination of medications that act at different points in the pain pathway may be beneficial. Nonpharmacological measures may also help patients and include active coping strategies; rest, ice, compression, and elevation; complementary therapies; and physiotherapy. Joint aspiration may also reduce acute joint pain, and joint steroid injections may alleviate chronic pain. In the longer term, increasing use of prophylaxis or performing surgery may be necessary to reduce the burden of pain caused by the degenerative effects of repeated bleeds. Whichever treatment option is chosen, it is important to monitor pain and adjust patient management accordingly. Beyond specific pain management approaches, ongoing collaboration between multidisciplinary teams, which should include physiotherapists and pain specialists, may improve outcomes for patients.

Pain relief for women with cervical intraepithelial neoplasia undergoing colposcopy treatment.

Pain relief for women with cervical intraepithelial neoplasia undergoing colposcopy treatment.

Conhecimento e atitude dos profissionais de enfermagem sobre avaliação e tratamento da dor neonatal

Objetivo do estudo foi verificar o conhecimento e atitude dos profissionais de enfermagem de uma unidade neonatal quanto à avaliação e tratamento da dor aguda em recém-nascidos. Estudo descritivo exploratório realizado com 26 profissionais de enfermagem de uma unidade neonatal no Centro-Oeste, Brasil. A maioria dos profissionais identificou ao menos uma escala de avaliação da dor neonatal (76,9%). As estratégias para alívio da dor selecionadas pelos profissionais foram diminuição de ruído e luminosidade (84,6%), posição canguru (76,9%) e colo (76,9%). Menos da metade (28,0%) dos profissionais afirmou registrar sempre ou frequentemente o escore de dor no plantão, e 64,0% referiu utilizar estratégias de alívio da dor. A maioria dos profissionais demonstrou conhecimento quanto ao manejo da dor, apesar de existirem lacunas. A aplicação das escalas e medidas de alívio da dor mostrou-se inadequada, seja pelo pouco uso, não utilização da melhor evidência disponível ou falta de registro.

From syntagmatic to paradigmatic spatial zeroes: The loss of the prepositionsein inner Asia Minor Greek

AbstractWe trace the diachronic development of the prepositionsein inner Asia Minor Greek from its use to mark a range of spatial functions to its ultimate loss and replacement by zero. We propose that, before spreading to all syntactic and semantic contexts, zero-marking was contextually-dependent on the presence/absence of a prenominal genitive modifying the head noun of Ground-encoding NPs and on the presence/absence of Region-encoding postpositions. We attribute these developments to an informational load relief strategy aimed at producing more economical utterances, as well as to language contact with Turkish, which favored structural convergence on the adpositional level between the two languages.

Effects of oral motor exercises and laser therapy on chronic temporomandibular disorders: a randomized study with follow-up.

This study investigated the efficacy of combining low-level laser therapy (LLLT) with oral motor exercises (OM-exercises) for rehabilitation of patients with chronic temporomandibular disorders (TMDs). Eighty-two patients with chronic TMD and 20 healthy subjects (control group) participated in the study. Patients were randomly assigned to treatment groups: GI (LLLT + OM exercises), GII (orofacial myofunctional therapy-OMT-which contains pain relief strategies and OM-exercises), and GIII (LLLT placebo + OM-exercises) and GIV (LLLT). LLLT (AsGaAl; 780-nm wavelength; average power of 60mW, 40s, and 60 ± 1.0J/cm²) was used to promote analgesia, while OM-exercises were used to reestablish the orofacial functions. Evaluations at baseline (T1), after treatment immediate (T2), and at follow-up (T3) were muscle and joint tenderness to palpation, TMD severity, and orofacial myofunctional status. There was a significant improvement in outcome measures in all treated groups with stability at follow-up (Friedman test, P < 0.05), but GIV did not show difference in orofacial functions after LLLT (P > 0.05). Intergroup comparisons showed that all treated groups had no difference in tenderness to palpation of temporal muscle compared to GC at follow-up (Kruskal-Wallis test, P < 0.01). Moreover, GI, GII, and GIII showed no difference from GC in orofacial functional condition (T2 and T3) while they differed significantly from GIV (P < 0.01). In conclusion, LLLT combined with OM-exercises was more effective in promoting TMD rehabilitation than LLLT alone was. Similar treatment results were verified with the OMT protocol.

Loin Pain Haematuria Syndrome - A Narrative Review of Pain Management Strategies.

Loin pain haematuria syndrome (LPHS) is an uncommon clinical entity that has divided renal physicians, pain practitioners, and even psychiatrists since its initial description. A relative paucity of data exists regarding the condition, with best practice guidelines lacking amid the existing threads of anecdotal experiences and variable follow-up observations. The aim of this article was to review the cumulative published experience of pain relief strategies for LPHS.

Involvement of opioid receptors in the systemic and peripheral antinociceptive actions of montelukast in the animal models of pain

This study aimed to investigate the involvement of opioid receptors in the systemic and peripheral antinociceptive activities of montelukast in different animal models of pain.Rats and mice were injected with montelukast to produce analgesia. The formalin and acetic acid-induced writhing tests were used to assess the nociceptive activity. The results showed that i.p. administration of montelukast (0.3–10mg/kg) dose-dependently reduced flinching behavior in both the first and second phases of formalin test with mean ED50 of 0.55 and 5.31mg/kg, respectively. Also, intraplantar administration of montelukast (3–30μg/paw) produced antinociception against the two phases of formalin assay in a dose-dependent way with mean ED30 of 2.92 and 8.11μg/paw, respectively. Furthermore, pre-treatment with naloxone (a non-selective opioid receptor antagonist) significantly inhibited both the systemic and also peripheral antinociceptive actions of montelukast in formalin test. In writhing test, the results showed that intraperitoneal administration of montelukast (3–10mg/kg) significantly reduced the writhe number induced by acetic acid in mice. Moreover, co-administration of non-effective doses of montelukast (0.3 and 1mg/kg; i.p.) and morphine (0.25mg/kg; i.p.) significantly decreased the writhes number induced by acetic acid. Also, this effect was naloxone-reversible. These findings suggest that the systemic and peripheral antinociception produced by montelukast were mediated through the opioid receptors in central and peripheral nervous systems. Moreover, combination of montelukast and morphine could be noted as a new strategy for pain relief.

SIRPα1-SHP2 Interaction Regulates Complete Freund Adjuvant-Induced Inflammatory Pain via Src-Dependent GluN2B Phosphorylation in Rats.

The elusiveness of pain mechanisms is a major impediment in developing effective clinical treatments. We examined whether the signal regulatory protein α1 (SIRPα1)-activated spinal Src homology-2 domain-containing protein tyrosine phosphatase 2 (SHP2)/Src cascade and the downstream GluN2B phosphorylation play a role in inflammatory pain. At hour 3 and days 1, 3, 5, and 10 after the intraplantar injection of complete Freund adjuvant (CFA), we assessed paw withdrawal latency using the Hargreaves test and analyzed dorsal horn samples (L4-L5) by Western blotting and immunoprecipitation. Intraplantar CFA injection provoked the behavioral hyperalgesia in the ipsilateral hind-paw along with SIRPα1, phosphorylated SHP2 (pSHP2), phosphorylated Src (pSrc), and phosphorylated GluN2B expressions and total SHP2 (tSHP2)-SIRPα1/pSHP2/pSrc and total Src (tSrc)-SIRPα1/pSHP2/pSrc coprecipitation in the ipsilateral dorsal horn. Although both of them failed to show an effect on CFA-enhanced SIRPα1 expression, spinal administration with SIRPα1-neutralizing antibody (10, 50, and 100 μg, 10 μL) and 8-Hydroxy-7-[(6-sulfo-2-naphthyl)azo]-5-quinolinesulfonic acid (NSC 8787; an SHP2 antagonist, 1, 10, and 100 μM, 10 μL) dose-dependently attenuated the behavioral hyperalgesia, SHP2 and Src phosphorylation, and tSHP2-SIRPα1/pSHP2/pSrc coprecipitation at day 1 after CFA injection. Intrathecal application of 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2; a Src-family kinase inhibitor, 10, 30, and 50 nM, 10 μL) exhibited a similar effect as these agents, except that it failed to ameliorate CFA-enhanced SHP2 phosphorylation and tSHP2-SIRPα1/pSHP2 coprecipitation. CFA-induced spinal SIRPα1 expression, which triggers SHP2, and Src phosphorylation, which subsequently induced pSrc-GluN2B interaction to mediate the GluN2B activation, contribute to spinal plasticity underlying the maintenance of inflammatory pain. These findings provide a possible strategy for pain relief by targeting to spinal SIRPα1-SHP2 coupling.

Stroke injury, cognitive impairment and vascular dementia

The global burden of ischaemic strokes is almost 4-fold greater than haemorrhagic strokes. Current evidence suggests that 25–30% of ischaemic stroke survivors develop immediate or delayed vascular cognitive impairment (VCI) or vascular dementia (VaD). Dementia after stroke injury may encompass all types of cognitive disorders. States of cognitive dysfunction before the index stroke are described under the umbrella of pre-stroke dementia, which may entail vascular changes as well as insidious neurodegenerative processes. Risk factors for cognitive impairment and dementia after stroke are multifactorial including older age, family history, genetic variants, low educational status, vascular comorbidities, prior transient ischaemic attack or recurrent stroke and depressive illness. Neuroimaging determinants of dementia after stroke comprise silent brain infarcts, white matter changes, lacunar infarcts and medial temporal lobe atrophy. Until recently, the neuropathology of dementia after stroke was poorly defined. Most of post-stroke dementia is consistent with VaD involving multiple substrates. Microinfarction, microvascular changes related to blood–brain barrier damage, focal neuronal atrophy and low burden of co-existing neurodegenerative pathology appear key substrates of dementia after stroke injury. The elucidation of mechanisms of dementia after stroke injury will enable establishment of effective strategy for symptomatic relief and prevention. Controlling vascular disease risk factors is essential to reduce the burden of cognitive dysfunction after stroke. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.

Postoperative analgesia after laparoscopic cholecystectomy by preemptive use of intravenous paracetamol or ketorolac: A comparative study

Background: Laparoscopic cholecystectomy is associated with postoperative pain due operative ports site and residual intraperitoneal gas CO 2 . Preemptive analgesia is one of the promising strategies of postoperative pain relief. The present study is undertaken to compare the efficacy of preemptive intravenous paracetamol versus ketorolac for post operative analgesia after laparoscopic cholecystectomy. Method: Ninety adult consented patients 18-58 yr of age, of either sex, of ASA grade I/II were randomized into two equal groups of 45 patients each. Patients of group I received infusion of paracetamol 1 g and group II received infusion of ketorolac 30 mg, 30 minutes before the induction of general anaesthesia. Postoperative pain was evaluated by standard 10 cm linear visual analogue scale at different time intervals. When VAS was more than 3 rescue analgesic 50 mg tramadol intravenously stat was given. Intraoperative hemodynamic and any side effects were also recorded for statistical analysis. Results: Demographic profile and hemodynamic parameters i.e intraoperative heart rate and mean arterial blood pressure were comparable in both the groups. Post operative VAS scores were persistently higher in paracetamol group with statistically significant difference (P value < 0.05). All 45 patients in paracetamol group and 8 patients in ketorolac group required rescue analgesic within 6 hrs of study time. Total tramadol consumption was much higher (2250 mg) in paracetamol group as compared to 400 mg in ketorolac group. Conclusion: Preemptive use of ketorolac exerted superior postoperative analgesia after laparoscopic cholecystectomy in comparison to paracetamol without any significant side effect.

Evaluation of pain of neonates during invasive procedures in intensive care

BACKGROUND AND OBJECTIVES: Neonates do not verbalize pain, so it is up to health professionals involved with their assistance to be qualified to evaluate pain during invasive procedures to plan relief strategies. This study aimed at evaluating pain in neonates admitted to a neonatal intensive care unit during invasive procedures. METHODS: Crossover investigation with 34 neonates admitted to the intensive care unit of a general hospital, from December/2012 to February/2013. Data were collected with the Neonatal Infant Pain Scale and analyzed by descriptive statistics. RESULTS: Procedures triggering more pain were tracheal tube aspiration, airways and venous puncture. Babies had severe pain during tracheal intubation and passage of peripheral insertion central catheter. CONCLUSION: Evaluating pain as the fifth vital sign with validated scale during invasive procedures is critical for planning and implementing ethic and humanized nursing assistance.

A Spinal Circuit for Mechanically-Evoked Itch

A satisfactory neurobiological understanding of itch has proved difficult to reach. Bourane et al. have now uncovered a previously unrecognized spinal circuit for mechanically-induced itch and elucidated a mechanism that keeps it in check. Dysregulation of this circuit could contribute to chronic itch, suggesting a new strategy for itch relief.

Fbxo3-Dependent Fbxl2 Ubiquitination Mediates Neuropathic Allodynia through the TRAF2/TNIK/GluR1 Cascade.

TNF-α participates in neuropathic pain development by facilitating the spinal TRAF2-dependent TNIK-GluR1 association, which drives GluR1-containing AMPA receptor trafficking toward the plasma membrane. In addition, F-box protein 3 modifies this pathway by inhibiting F-box and leucine-rich repeat protein 2-mediated TRAF2 ubiquitination, suggesting that protein ubiquitination contributes crucially to the development of neuropathic pain. These results provide a novel therapeutic strategy for pain relief.

Workload Pressures of Principals

This study is designed to understand how principals perceive the common stressors associated with leading an educational enterprise and propose strategies for relief from job-related stressors. As such, the same survey results from principals in 2009 and 2012 are analyzed. The results indicated increases in the perceived state of stress with regard to personal stress and factors that have been associated with new legislative demands on principals. To that end, the authors identified sources of renewal for principals experiencing workplace stress that include mindfulness practice to help school leaders thrive at work.

Ability of the Pain Recognition and Treatment (PRT) Protocol to Reduce Expressions of Pain among Institutionalized Residents with Dementia: A Cluster Randomized Controlled Trial

Many strategies have been used to improve pain management in institutionalized care settings, but there is no consensus on the effects of these methods. The study purpose was to compare the effect of a Pain Recognition and Treatment (PRT) protocol coupled with basic pain education (experimental group) versus basic pain education alone (control group) in (1) improving the pain management performance of registered nurses (RNs) and (2) reducing pain-related expressions of residents with dementia postintervention and at 3-month follow up. A double-blind cluster randomized controlled trial with a 3-month follow-up period was conducted with 195 residents of six dementia special-care units. The weekly pain management performance of RNs (e.g., use of pharmacologic and nonpharmacologic strategies, use of referral) was recorded and weekly average scores of the pain-related expressions of residents were assessed using the following: the Verbal Descriptor Scale (VDS), Pain Assessment in Advanced Dementia Scale (PAINAD), and the Cohen-Mansfield Agitation Inventory (CMAI). The generalized linear mixed model analysis showed that, after intervention, the experimental group had significantly more weekly nonpharmacologic pain relief strategies and weekly referrals for pain management than the control group. Residents in the experimental group had significantly fewer verbal and behavioral expressions of pain compared to those in the control group. However, the groups did not differ significantly in the use of pharmacological strategies or the agitated behaviors expressed by residents. The PRT protocol is effective and is recommended for routine use in residents with dementia to improve the quality of pain care.

VPS26A-SNX27 Interaction-Dependent mGluR5 Recycling in Dorsal Horn Neurons Mediates Neuropathic Pain in Rats.

VPS26A-SNX27-dependent mGluR5 recycling plays a role in the development of neuropathic pain. The regulation of the VPS26A-SNX27 interaction that modifies mGluR5 trafficking and expression in the dorsal horn provides a novel therapeutic strategy for pain relief.