Role In Pain Management Research Articles

Efficacy of pregabalin in management of postoperative pain and functional outcomes in immediate postoperative period following total knee replacement

Introduction: Immediate postoperative pain after total knee arthroplasty has remained a serious problem, which prolongs the length of hospital stay and functional recovery. Thus multimodal pain management protocol are followed in these patients. Our study aims to assess the efficacy of pregabalin use in pain management and functional recovery of patients in the immediate postoperative period. Materials and Methods: We did a prospective randomised case control study by taking patients operated for total knee arthroplasty and receiving multimodal analgesia. We divided them into two groups with 100 patients in each group. GROUP A (with pregabalin) AND GROUP B (without pregabalin). We have given Pregabalin in recommended and FDA approved safe dosage of 75 mg one tab bedtime for a period of three weeks postoperatively along with selective COX-II inhibitors NSAIDs, (celecoxib) for three weeks. In another group, we have omitted the use of pregabalin and gave only celecoxib for three weeks. Patients were assessed by knee society score, WOMAC score, and VAS scores at 24 hr after surgery, 48 hr after surgery, at two weeks. Results: The patients were divided into two groups each having 100 patients and were compared using statistical tools using one way ANOVA Test, The Vas Score, WOMAC Score, knee Range of motion and Knee Society Score showed statistically significant change in pregabalin group. Discussion: We are performing this comparative study to assess its role in pain management and also its effects on functional outcomes of the patient. Few literature suggests that Pregabalin is effective for reducing opioid consumption after primary TKA and reducing respiratory, renal, and hemodynamic complications. Conclusion: In my study the use of Pregabalin is suggestive of improvement in pain score and functional outcomes in the patients in immediate post-op period over 3 months. However, future studies regarding doses and pregabalin medication are required.

A physical therapist’s role in pain management: A biopsychosocial perspective

AbstractAimPeople suffering with chronic pain have a decreased quality of life in both the physical and psychosocial dimensions. Popular treatment methods for a chronic pain patient are opioid prescriptions and surgery, which may not be beneficial to long‐term outcomes in chronic pain patients, and may actually result in reducing a patient's overall health.PurposeThis review will examine the role of the physical therapist in treating chronic pain patients in regard to the biopsychosocial model. Reviewing chronic pain through a biopsychosocial perspective, screening, evaluation, intervention selection, and problems with programs adherence in regard to chronic pain patients in physical therapy will be discussed. Psychosocial components of chronic pain including fear of movement and depression are also examined in how they can hinder or interfere with physical therapy treatment and evaluation.ConclusionWhen treating chronic pain patients, applying the biopsychosocial perspective to physical therapy with a focus on restoring physical function could provide the least invasive treatment for chronic pain patients with optimal outcomes.

Family Members’ Experiences with Observing Pain Behaviors Using the Critical-Care Pain Observation Tool

BackgroundCurrent guidelines support family members' participation in care, but little is known regarding their potential contribution to pain assessment using validated behavioral pain scales. AimsThis study aimed to describe family members’ observations of pain behaviors with the Critical-Care Pain Observation Tool and their evaluation of the tool and its use, and to understand their experience and perceptions of their potential role in pain management in the intensive care unit. DesignA mixed methods cross-sectional explanatory design was used. SettingA medical-surgical intensive care unit in Canada. Participants/SubjectsFamily members were eligible if they had a loved one admitted in the intensive care unit who was unable to self-report. MethodsFamily members identified pain behaviors using the Critical-Care Pain Observation Tool after a brief training, completed a self-administered questionnaire, and participated in a follow-up individual interview regarding their experience and perceived potential role in pain management when their loved one is unable to self-report. ResultsTen family members participated. A 15-minute training appeared sufficient for family members to be comfortable with observing pain behaviors included in the Critical-Care Pain Observation Tool. The tool allowed them to confirm their observations of pain behaviors, to focus more on the patient, and to advocate for better pain management. ConclusionsFuture research is needed to explore the views of more family members and to compare their Critical-Care Pain Observation Tool scores to the ones of nurses' for interrater reliability testing.

Challenges faced with opioid prescriptions in the community setting - Australian pharmacists' perspectives.

Prescription opioids (POs) are well recognised for their role in pain management. However over recent years, use of POs has become an increasingly complex public health issue, with the emergence of increasing quantities of POs being misused and abused. Pharmacists represent the 'gatekeepers' of medicines, which can be a challenging role, relating in particular to POs. This study aimed to gain insight into the challenges Australian community pharmacists experience in the dispensation of POs. Sydney Australia. Twenty-five pharmacists were recruited from suburbs in and around Sydney, Australia. Pharmacists were interviewed using an in-depth, semi-structured protocol. All interviews were audio-recorded, transcribed and thematically analysed. Identification of issues/factors that may influence the dispensing of POs. Pharmacists were reportedly confronted with several issues in the dispensing of POs, particularly in relation to the patient and prescriber. Pharmacists reported some individuals becoming increasingly more "creative" in the methods used to obtain POs, rendering detection of potential abuse/misuse increasingly difficult. Poor professional relationships with prescribers-an apparent power dynamic between the two professions, and limited engagement with patients were issues also identified. The majority of participants suggested that an electronic monitoring database would help in the identification of PO abuse/misuse. Education is required to emphasise the importance of inter-professional collaboration between pharmacists and prescribers, as is empathy in the pharmacist-patient relationship. Prescription drug monitoring programs and prescribers sending electronic prescriptions directly to the pharmacist were perceived as helpful initiatives to undertake.

Nurses Knowledge Regarding Post-operative Pain Management

Objective: The aim of this study was to explore nurses’ knowledge regarding postoperative pain management Background: Effective management of pain in hospitalized patients is an important aspect of quality care delivery, optimal clinical outcomes and patient satisfaction. Nurses play an important role in pain management but it has been widely observed that nurses have limited knowledge about management of post-surgical pain. Methodology: A quantitative descriptive cross-sectional study was conducted in a private tertiary care hospital in Peshawar, Pakistan. Study included nurses working at bedside in post-operative units of the hospital. A self-developed questionnaire was used for data collection. Chi square test was used to analyse the data. Results: The level of knowledge was divided into poor, average, good and excellent categories. Percentage score of categories was, poor (0%); average (6.7%); good (71.7%); and excellent (21.7%). Conclusion: Current study showed that majority of nurses working in surgical units had good knowledge of post-operative pain management. The focus of current study was on the exploration of nurses’ knowledge regarding post-operative pain management, further studies need to be conducted to explore barriers and factors affecting their knowledge regarding post-operative pain management.

Evidence-based position paper on Physical and Rehabilitation Medicine professional practice for persons with acute and chronic pain. The European PRM position (UEMS PRM Section).

Pain is a frequent complaint from patients undergoing rehabilitation. It can be a major problem and can lead to several activity limitations and participation restrictions. For this reason, when the Professional Practice Committee (PPC) of the Physical and Rehabilitation Medicine (PRM) Section of the European Union of Medical Specialists (UEMS) decided to prepare evidence-based practice position papers (EBPPs) on the most relevant fields of PRM, a paper on the role of the PRM specialist on pain conditions was also included. The goals of this paper are to provide recommendations on the PRM physician's role in pain management; how to address this major problem and what is the best evidence-based approach for the PRM physician in acute and chronic pain conditions. This paper follows the methodology defined by the Professional Practice Committee of the UEMS-PRM Section. A systematic literature search in PubMed was carried out and the results obtained from filtered papers were subjected to four Delphi rounds. Fifteen recommendations were obtained from the Consensus Process and systematic review and were approved by all of the delegates of the UEMS-PRM Section. It is recommended that PRM physicians focus on pain as a primary aim of their interventions, in whatever field they are applying their competencies. It is also recommended that the approach to pain focuses either on reducing the symptoms and improving functioning/reducing disability or recurrences and improving the health condition in the long term avoiding chronicity. Every PRM specialist encounters the problem of pain and some specialize in this field and their role is greater than that of the regular PRM doctor. Based on the evidence available, it is reasonable to determine the role of the physiatrist in managing pain.

Clinical diagnosis and treatment for iliotibial band syndrome

As an usually occurs in athletes, iliotibial band syndrome is payed more attention for people, the disease is diagnosed mainly by clinical symptoms, physical examination and MRI, but there is no uniform diagnostic criteria. The pathogenesis of iliotibial band syndrome is considered to be related to pressure and friction factors. As for the treatment, manipulation, muscle exercise, mainly drugs and physical therapy and so on both at home and abroad are recognized to use to achieve desired effect. For conservative failure, refractory iliotibial band syndrome patients, arthroscopy, or release of iliotibial band syndrome surgery are performed. While conservative local drug injection combined with muscle exercise could play a role in pain management besides, arthroscopic as operation method is more advanced, and applicable to all types of patients without absolute contraindication, so it is helpful for patients with early activity. At present, there is still a great deal of controversy about its pathogenesis, and there is no obvious limit for the specific indications of its various therapies in clinic, so it needs further specification.

C13 Chiropractic Medicine's Role in Pain Management for Cancer Patients

Integrative oncology continues to evolve as an evidence-based specialty. The use of complementary therapies in concert with medical treatment creates efficacy, improves symptom control, alleviates patient distress and reduces suffering. Patients, gravitate toward alternative treatments like chiropractic care to help with quality of life, especially when standard cancer treatments fail. The aim of this program is to explain how chiropractic can be used to manage cancer pain safely and efficiently while creating clinical team alliances.

The importance of nurse monitoring for potential opioid abuse in their patients

Deaths related to opioids have quadrupled since 1999, making it a top priority in health care. This article will provide an overview of the opioid crisis, focusing on the role that nurses play in addressing this crisis, with emphasis on assessment, early recognition, and prevention of opioid misuse. Systematic review of Medline, PubMed, and Google Scholar for articles relating to nurses’ role in pain management, education, and safe opioid use. Research suggests the incidence of ongoing, persistent pain is at an all‐time high (IOM Report, 2011, Relieving pain in America: A blueprint for transforming prevention, care, education, and research, The National Academies Press, Washington, DC), coincidently the rate of opioid prescribing over the past 15 years has also reached an all‐time high (Prescription Opioid Overdose Data, 2017, https://www.cdc.gov/drugoverdose/data/overdose.html/). An “opioid crisis” was declared, calling for safer opioid prescribing (CDC Guideline for Prescribing, 2016, https://www.cdc.gov/mmwr/volumes/65/rr/rr6501e1.htm/). Further research shows that nurses are educated and accomplished health care professionals (ASPMN, 2017, The core curriculum for pain management nursing, Elsevier, New York, NY; DEA Requirements, 2017, https://www.deadiversion.usdoj.gov/pubs/docs/dwp_buprenorphine.htm/; Ray & Behr, Clinical Nurse Specialist, 31, 2017, 115; St. Marie, Pain Management Nursing, 17, 2016, 311), at the forefront of monitoring for addiction and opioid misuse. Nurses contribute greatly to enhanced pain assessment and education to patients, families, and their peers. With the current opioid crisis, nurses have taken on the added responsibility of monitoring for potential opioid abuse, safety, and signs of addiction in their patients.

Oncology nurse reflection on the necessity of a pain assessment tool for Indonesian cancer patients

The purpose of this study was to obtain an overview on nurses' opinions and perceptions related to pain assessment and other problems experienced in evaluating pain in cancer patients. This descriptive qualitative study was part of a series of studies to develop a pain assessment tool for cancer patients in Indonesia. Data were collected by semi-structured interviews from 16 oncology nurses. A cross-case comparison of the interview responses was used to analyze the data from verbatim interview transcripts. Six themes were identified: pain as the main complaint reported by cancer patients; pain assessment using a pain scale; an awareness of the absence of nurses' role in pain management; a lack of understanding of pain conditions; acknowledgement that a pain assessment tool should be practical and user friendly; and the need to develop a pain assessment tool. We also explored the knowledge of nurses in pain management and achieved an in-depth understanding of the nurses' desire to seek additional knowledge related to pain assessment. A pain assessment tool should be developed to assist nurses to independently interpret data about pain and allow them to select or modify interventions consistent with the patients' needs. Pain management for cancer patients is one of the essential nurses' responsibilities in providing comprehensive meaningful nursing care.

Nursing pain experts in German hospitals : A compilation of activity profiles and tasks

In recent years nurses have come to play aprofessional role in pain management. In Germany, the publication of the national expert standards on pain management in nursing resulted in nurses being educated to be pain resource nurses; however, since education has started the continuance and commitments of specialized pain nurses in clinical practice is basically unclear. The goal of this evaluation was to identify how pain resource nurses are involved in pain management and organizational aspects in German hospitals. Online survey of 374directors of nursing services of different types of hospitals on the assignment of nursing pain experts. Pain resource nurses are involved in pain management in 70.6% of the hospitals responding to the questionnaire. Their task profile depends on the hospital size and 42.2% of the hospitals have documented task profiles. Pain resource nurses are primarily involved in invasive pain management processes (37.1%) and in the management of pain in patients with complex pain problems after surgery (33.2%). Educative tasks are training of colleagues and implementation and conversion of the national expert standards. Of the hospitals 36.1% implemented the national expert standards for acute pain and 57% of the medium-sized hospitals have at least also implemented the national expert standards for chronic pain. The study shows afirst insight into the task profiles of pain resource nurses. The implementation of this special qualification is meaningful and seems to be well-recognized in the hospitals. The tasks of patient care are orientated to the spectrum of patients treated in the hospital. The tasks of education also show the importance for the education of colleagues.

Biochemical, Oxidative, and Physiological Changes Caused by Acute Exposure of Fentanyl and Its 3 Analogs in Rodents.

Synthesis and bioefficacy of fentanyl and its 8 new 1-substituted analogs (1-8) were earlier reported by us. Of these 8 compounds, N-(1-(2-phenoxyethyl)-4-piperidinyl)propionanilide (2), N-isopropyl-3-(4-( N-phenylpropionamido)piperidin-1-yl)propanamide (5), and N- t-butyl-3-(4-( N-phenylpropionamido)piperidin-1-yl) propanamide (6) were found to be more effective and less toxic compared to fentanyl. The present study reports the acute effect of fentanyl (0.50 Median Lethal Dose (LD50); intraperitoneal) and its 3 analogs (2, 5, and 6) on various biochemical and oxidative parameters in mice and various physiological parameters in rats. Blood alkaline phosphatase (1 hour and 7 days) and urea levels (1 hour) were significantly elevated by fentanyl, while alanine aminotransferase levels (1 hour) were increased by both fentanyl and analog 2 compared to the corresponding control. Increase in partial pressure of carbon dioxide and decrease in partial pressure of oxygen were also caused by fentanyl and analog 2 (1 hour). Analog 6 alone elevated malondialdehyde levels in the brain, liver, and kidney tissues (7 days). The LD50 of fentanyl and analogs 2, 5, and 6 were found to be 0.879, 87.88, 69.80, and 55.44 mg/kg, respectively, in rats. Significant decrease in heart rate, mean arterial pressure, respiratory rate (RR), and neuromuscular transmission was produced by fentanyl and analog 2, while analog 5 decreased the RR alone. The changes, particularly the respiratory depression, were found to be reversed by naloxone, a μ-receptor antagonist. Thereby, indicating involvement of μ-receptor mediated effects of the compounds. To conclude, all the analogs were found to be less toxic compared to fentanyl, suggesting their possible role in pain management.

A35 TRNS effects on multiple sclerosis symptoms: A randomized double-blind sham-controlled trial

Objectives Nowadays, there is a growing interest in investigating the potential role of noninvasive brain stimulation (NIBS) techniques in several neuropsychiatric diseases. Among the latter, multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system, can result in a variety of difficult-to-treat symptoms. The aim of this work is to assess the effects of transcranial random noise stimulation (tRNS), an NIBS technique, on frequently encountered and challenging MS-related symptoms, namely neuropathic pain, cognition, mood, and fatigue. Methods 16 MS patients were enrolled. Each patient randomly underwent two stimulation blocks (active or sham) over the left dorsolateral prefrontal cortex. Each block consisted of three consecutive daily sessions. The evaluation consisted of the Attention Network Test, Visual Analogue Scale for pain, Neuropathic Pain Inventory, Hospital Anxiety and Depression Scale, Modified Fatigue Impact Scale, as well as neurophysiological measures for pain and cognition (Pain related evoked potentials, frontal midline theta activity). Results Compared to sham stimulation, a trend towards pain improvement was obtained following the active tRNS as documented by a decrease in pain scores and N2-P2 amplitudes of pain related evoked potentials. Active tRNS did not have any effects on frontal midline theta activity, attention, mood or fatigue scales. Discussion The absence of effects on other symptoms might be related to sample size and short protocol duration. Conclusions tRNS seem to induce analgesic effects in MS related neuropathic pain. Significance tRNS might play an important role in pain management especially in situations where pharmaceutical agents are faced with limited benefits.

Videogames as Therapy

There is a long history of using videogames in a therapeutic capacity including rehabilitation for stroke patients, people with traumatic brain injuries, burns victims, wheelchair users, Erb's palsy sufferers, children undergoing chemotherapy, children with muscular dystrophy, autistic children and individuals looking to overcome real-life challenges (including symptoms of depression) and boost their wellbeing (including boosting life satisfaction, self-efficacy and social support). This paper briefly and selectively examines a number of areas including: (1) videogames as physiotherapy and occupational therapy, (2) videogames as distractors in the role of pain management, (3) videogames and cognitive rehabilitation, (4) videogames and the development of social and communication skills among the learning disabled, (5) videogames and impulsivity/attention deficit disorders, (6) videogames and therapeutic benefits in the elderly, (7) videogames in psychotherapeutic settings, (8) videogames and health care, (9) videogames and anxiety disorders, and (10) videogames and psychological wellbeing. It is concluded that there has been considerable success when games are specifically designed to address a specific problem or to teach a certain skill. However, generalizability outside the game-playing situation remains an important consideration.

Influencing Nursing Knowledge and Attitudes to Positively Affect Care of Patients with Persistent Pain in the Hospital Setting

Hospitalized patients with persistent pain are among the most challenging populations to effectively manage because of coexistence with acute pain. Nurses play a vital role in pain management; however, gaps in knowledge and detrimental attitudes exist. The purpose of this study was to evaluate the effectiveness of a targeted evidence-based pain education program to increase nurses’ knowledge and attitudes about pain management. One group, paired, pretest/posttest educational intervention. A convenience sample of nurses from three medical and surgical inpatient units were recruited. Participants completed a pretest, the Knowledge and Attitudes Survey Regarding Pain Scale, to assess education needs. Identified gaps were targeted during program design. The program consisted of two 30-minute interactive educational sessions approximately 1 month apart. The first session, delivered by a pharmacist, covered pharmacology and pathophysiology content. The second session, delivered by trained registered nurses, used case studies paired with video scenarios. A total of 51 nurses completed the pretest. The final sample consisted of 24 nurses who completed both the pretest and posttest. The mean age was 30 years; 88% were female, and 92% were baccalaureate prepared. Paired t tests indicated higher posttest total scores (p < .001) after the education program compared with pretest scores. Overall program satisfaction was positive. This study found improvement in persistent pain management knowledge and attitudes among direct care nurses caring for hospitalized patients. A targeted educational program may be an effective and efficient delivery method.

Chiropractic Medicine's Role in Pain Management for Cancer Patients

Chiropractic Medicine's Role in Pain Management for Cancer Patients

An industry perspective on pain treatment in the UK.

Jan-Uwe Claas and Mark Suett speak to Henry Ireland, Senior Drug Evaluations Editor: Dr Jan-Uwe Claas, General Manager, Grϋnenthal UK Ltd, and Dr Mark Suett, Interim Medical Director, discuss Grϋnenthal's role in pain management, the current barriers to improving treatment in the UK and the supporting role the company plays in advancing this field. Grünenthal UK Ltd is a subsidiary of Grünenthal GmbH, based in Aachen, Germany.

Association between lymphocyte expression of the apoptotic receptor Fas and pain in critically ill patients.

ObjectiveLymphocyte apoptosis in critical illness is associated with immunosuppression. We explored for the first time the associations between pain ratings and expression of the apoptotic receptor Fas on B and T cells in critically ill patients and the potential mediating effects of adrenocorticotropic hormone (ACTH), cortisol, and substance P (SP).DesignThis is an exploratory correlational study with repeated measurements (14 days followup) and cross-sectional comparisons.SettingThis study was conducted in a state hospital in the metropolitan area of Athens, Greece.ParticipantsThe participants were 36 consecutive critically ill patients and 36 matched controls.Outcome measuresPain measured by the self-reported numeric rating scale [NRS], the behavioral pain scale, and the pain assessment scale was the primary outcome measure. Flow cytometry (Fas), electrochemiluminescence (ACTH and cortisol) and enzyme-linked immunosorbent assay (SP) were used. Mixed linear models for repeated measurements and bivariable associations at discrete time points were employed.ResultsSignificant pain at rest was noted. Pain ratings associated with Fas expression on cytotoxic T cells (P=0.041) and B cells (P=0.005), even after adjustment for a number of clinical treatment factors (P=0.006 and P=0.052, respectively). On the day that more patients were able to communicate, Fas on B cells (r=0.897, P=0.029) and cytotoxic T cells (r=0.832; P=0.037) associated with NRS ratings. Associations between pain ratings and ACTH serum levels were noted (P<0.05). When stress neuropeptide levels were added to the model, the statistical significance of the associations between pain ratings and Fas expression was attenuated (P=0.052–0.063), suggesting that stress neuropeptides may partially mediate the association.ConclusionPreliminary evidence for the association between pain and lymphocyte apoptotic susceptibility is provided. The role of pain management in maintaining immunocompetence in critical illness is worth exploring.

Experience of nurses about barriers to pain management in pediatric units: A qualitative study

Context: Children's pain in hospital settings has not yet been managed well. Although nurses play an important role in pain management, its extent is limited with respect to clinical nurses in Iran. Aims: This study was conducted to explore the experience of nurses' barriers to pain management in pediatric units. Settings and Design: This qualitative study was conducted at two teaching hospitals in Amirkola Children's Hospital in Babol and Children's Medical Centers in Tehran, Iran. Data were collected from 19 nurses, using unstructured and deep interviews during 2014–2015. Material and Methods: Sampling was purposeful with maximum variation. Data analyzed by conventional content analysis method simultaneously data collection based on five steps of Granheim and Lundman (2004). To ensure about the accuracy and reliability of data, four criteria namely credibility, confirmability, dependability, and transferability, were used according to Lincoln and Guba's criteria. Before the interviews, participants were ensured about the confidentiality of their information and voluntarily nature of the study. In addition, written informed consents of the nurses were obtained. Results: Data analysis extracted five themes of barriers to pain management, including: Inappropriate organizational structure, interruption in pain relief activities, inadequate competency of the nurses, individual characteristics of child and parents, and inefficacy of companions. These themes indicated the barriers to pediatric pain management based on research conditions and experience of nurses in the pediatric ward. Conclusions: Therefore, modification of organizational structure, elimination of causes of delay in pain relief measures, promotion of nursing competencies, paying attention to child and parents' characteristics, and improvement of companions' effectiveness should be prioritized to achieve an optimal pain management

The μ1-opioid receptor and 5-HT2A- and 5HT2C-serotonergic receptors of the locus coeruleus are critical in elaborating hypoalgesia induced by tonic and tonic–clonic seizures

It has been proposed that the post-ictal state is associated with the expression of hypoalgesia. It is clear that the projections among the periaqueductal gray matter (PAG), dorsal raphe nucleus (DRN) and locus coeruleus (LC) play a role in pain management. These mesencephalic structures have direct reciprocal opioid and monoaminergic projections to the LC that can possibly modulate post-ictal hypoalgesia. The goal of this study was to examine if LC-opioid and serotonergic/noradrenergic mechanisms signal the post-ictal hypoalgesic responses to tonic–clonic seizures produced by intraperitoneal administration of pentylenetetrazole (PTZ at 64mg/kg), causing an ionophore γ-aminobutyric acid (GABA)-mediated Cl− influx antagonism. The rodents’ nociceptive threshold was measured by the tail-flick test. Intra-LC cobalt chloride (1.0nM/0.2μL) microinjections produced intermittent local synaptic inhibition and were able to reduce post-ictal hypoalgesia. Central administration of naltrexone (a non-selective antagonist for opioid receptors), naloxonazine (a selective antagonist for μ1-opioid-receptors), methysergide (a non-selective antagonist for serotonergic receptors) or ketanserin (an antagonist for both α1-noradrenergic and 5-Hydroxytryptamine(HT)2A/2C receptors) at 5.0μg/0.2μL, R-96544 (a 5-HT2A receptor selective antagonist) at 10nM/0.2μL, or RS-102221 (a 5-HT2C receptor selective antagonist) at 0.15μg/0.2μL into the LC also decreased post-ictal hypoalgesia. The data presented here suggest that the post-ictal antinociception mechanism involves the μ1-opiod, 5-HT2A- and 5-HT2C-serotonergic, and α1-noradrenergic receptors in the LC.