Mixed Pain Syndromes Research Articles

Comparison of pharmacotherapeutic analgesic response and safety profile of tapentadol with other opioids.

Tapentadol is a unique opioid analgesic due to its dual mechanism of action. Compared to other opioids with a classical mechanism of action, its analgesic potential is not far behind them, and its advantages are: a better safety profile in terms of a lower potential for drug-drug interactions and a lower potential for causing adverse events, and it is safe to use in sensitive populations. Tapentadol in the form of a immediate release formulation is an adequate drug of choice for achieving a pharmacotherapeutic analgesic response in acute pain conditions, while in the form of a extended release formulation it is an adequate pharmacotherapeutic analgesic solution for chronic pain syndromes of various etiology. Due to the specificity of the mechanism of action, tapentadol adequately relieves both pain components - nociceptive and neuropathic, and has an indication area for mixed pain syndrome as well. Based on this, the need for the use of co-analgesics is reduced, and thus the incidence of possible interactions and adverse events is reduced.

“Prevalence of Pain Syndromes in the Oncological Patient”

Introduction: Pain is a common symptom in cancer patients, ranging from 24% to 86% depending on stage and type. It can be related to tumor cells, primary site, and metastases. This retrospective study aimed to identify painful syndromes, their etiology, and prescribed treatment, identifying complex pain syndromes difficult to treat and developing new pain management strategies for advanced cancer patients. Materials and Methods: A retrospective, observational, and descriptive study was conducted from August 1, 2020, to June 1, 2023. The review of patient records treated at the Pain Clinic was conducted, encompassing all the data routinely collected during each consultation. The SPSS 23 program was used to analyze the data. Results: Two hundrend and five patients who met the inclusion criteria were included. The most common oncological diagnosis was cervical cancer (29.8%); the study found that visceral pain syndrome (35.6%), somatic pain syndrome (33.2%), and mixed pain which was somatic and neuropatic (17.6%) are the most common algologic diagnostics. The average pain intensity for patients seen for the first time was 5.6 by ENA (n = 82) and the average pain intensity for subsecuent patients was 2.6 (n = 123). The most often prescribed treatment was weak opioids, with a 29.3% rate. Conclusion: The study population experienced visceral, mixed, and neuropathic pain syndromes due to cervical cancer diagnosis, with opioid therapy being the primary treatment, aligning with international pain management guidelines.

Pain Improvement Among Chronic Lumbar Disc Herniation Patients Underwent Epidural Triamcinolone With Or Without Hyaluronidase Injection Within 3 Months Of Follow-Up: A Prospective Study

Background Chronic lumbar disc herniation (CLDH) will accompany by chronic inflammation, so the fibrosis tissues formed in the epidural space and adjacent nerve roots, and lead to mixed pain syndrome. Objectives To compare between triamcinolone only and hyaluronidase 1500 international unit (IU) administration epidural injection for treating bulged or protrusion CLDH. Methods This prospective study involved CLDH patients visiting the outpatient department of Neurology at Dr. Kariadi Hospital Semarang Indonesia from November 2021 until August 2022. They divided: triamcinolone (Group 1) and hyaluronidase 1500 IU and triamcinolone epidural injection (Group 2) with 3 days of hospitalization. Neurotrophic was prescribed during 3 months of follow-up and ordered for personal physical treatment. They analyzed pain improvements (NRS and Pain DETECT), and the Oswestry Disability Index (ODI) scores. Results The 37 subjects were recruited but 1 female dropped out cause of re-injection, so 13 males and 23 females aged between 24 to 72 years old (mean 48+2) were followed. They significantly improved (Wilcoxon test p=.000), as the NRS score was 47.9% (Group 1) and 55.4% (Group 2). ODI scores without significance (Mann-Whitney p> .005), such at 2 weeks (group 1= 20.4%, group 2= 23.6%) and 3 months (group 1= 58.1%, group 2= 53.7%). They observed nociceptive and neuropathic improvement even though needed more time for the healing process. Conclussions This study proved hyaluronidase administration before triamcinolone epidural injection with better improvements for treating bulged or protrusion CLDH patients.

Nociceptive and Mixed Pain Syndromes in Patients with Multiple Sclerosis

Nociceptive and Mixed Pain Syndromes in Patients with Multiple Sclerosis

Etiopathogenetic substantiation of surgical treatment of neurogenic pain syndromes

The purpose of the study was to improve classification of neurogenic (neuropathic) pain syndromes. This will make it possible to define the indications for appropriate analgesic surgery for each type of drug-resistant neurogenic pain syndrome. Incorrect management of neurogenic pain syndromes is usually associated with underestimation of pathogenetic prerequisites for its occurrence. Differentiation of compression, deafferentation and mixed neurogenic pain syndromes makes it possible to determine appropriate surgery and avoid tactical errors. Moreover, this approach allows you to save patients from unreasonable long-standing suffering. Patients with chronic pain syndromes often become disabled, sometimes in the prime of life, and isolated from society and family. Therefore, treatment of chronic pain is currently an urgent problem.

Retrospective review of opioid use in pediatric patients with chronic pain

Background and Hypothesis: Demographics and treatment of adult patients with chronic pain have been well characterized. The same has not been done in pediatric patients who are at increased risk of the consequences of opioid use including risk of addiction, truancy, and unemployment. We hypothesize that opioid use in pediatric patients with chronic pain leads to worse functional outcomes due to pain and maladaptive behaviors.
 
 Methods: From 2016-2019, 300 new patient consultations to the Riley comprehensive pain clinic were identified. A subpopulation interim analysis of 71 patients was retrospectively evaluated at 6-month intervals for medical, social, pain-related, and questionnaire data. Data was recorded in REDCap by a single researcher. Exported data was analyzed using Microsoft Excel.
 
 Results: Seventy-one patients were evaluated and 80% were female. Median age at diagnosis was 14 years (range birth to 18) with average follow-up of 20.5 months. Etiologies varied but contributed to neuropathic (49%), nociceptive (35%), and mixed (11%) pain syndromes. Comorbid psychiatric disorders and sleeping difficulties were present in 69% and 58%, respectively. Sixty-seven percent of age-appropriate patients graduated high school and were in college or employed on final follow-up. Patients managed with opioids did not report a change in visual analog or catastrophizing scales.
 
 Conclusion and Potential Impact: The primary demographic of pediatric chronic pain patients is adolescent females. Neuropathic pain syndromes are common, with a majority of patients exhibiting comorbid psychiatric disorders and dysfunctional sleep patterns. Use of opioid medications did not change reported pain scores, and one-third of these chronic pain patients did not attend college or were unemployed. Further analysis of our data set should help better understand the outcomes of pediatric patients with chronic pain.

Nociceptive and mixed pains in patients with multiple sclerosis

Nociceptive and mixed pain syndromes (NMPS) whose pathogenesis is linked with the formation of plaques of demyelination in the CNS are commonly present in patients with multiple sclerosis (MS). NMPS of diverse locations, mechanisms and clinical features significantly worse patients' disability and impair their social adaptation. At the same time, clinicians do not pay enough attention to these syndromes in routine practice. Early diagnosis of NMPS may be important not only for early and appropriate NMPS' therapy and improvement of patients' quality of life, but, possibly, for the diagnosis of the onset or relapsing phase of MS, in cases when NMPS are the symptoms of MS and are the signs of active demyelinating process. This review addresses contemporary views of the main types of NMPS in MS (headaches, musculoskeletal pains, painful tonic spasms, pain with spasticity). Epidemiologic data, pathogenesis, clinical manifestations and diagnostic options of NMPS in patients with MS are described along with current views on MS and NMPS comorbidity theories. Existing approaches to treatment of NMPS based on randomized trials data are analyzed.

Combination therapy with methadone and duloxetine for cancer-related pain: a retrospective study.

A comprehensive approach to pain management often requires multimodal therapy and a combination of medications. Oncology patients may be prescribed methadone and duloxetine as single agents or in combination for cancer-related pain, particularly neuropathic pain. Duloxetine is also prescribed for depression or anxiety in patients with cancer. A retrospective chart review on patients with cancer-related pain prescribed duloxetine and methadone combination therapy at the Virginia Commonwealth University supportive care clinic (SCC) between 2012 and 2019. Edmonton Symptom Assessment System (ESAS) scores reported by patients on monotherapy were compared to scores after they started combination therapy. Of 131 patients identified on combination therapy, 43 met study criteria (2 with incomplete ESAS scores). ESAS total and subscores after combination therapy were lower than on monotherapy. Combination therapy decreased total, pain, and emotion subscores by 5.6 (SD =17.3, dz =-0.32, P=0.046), 0.9 (SD =3.0, dz =-0.30, P=0.052), and 1.8 (SD =5.1, dz =-0.36, P=0.023), respectively. On combination therapy, 28% of patients reported at least a two-point reduction in pain scores. All study participants reported cancer pain with neuropathic components; most had mixed pain syndromes comprising nociceptive and neuropathic components. Adherence rates were high as 81% of patients with follow-up appointments continued therapy. These results suggest the combination of duloxetine and methadone reduces cancer-related pain and emotional symptom burden compared to either medication as a single agent.

Pain Syndromes Other Than Headache

Pain is experienced within a complex biologic, emotional, psychological, and social context that may defy physical examination, diagnostic procedures, and laboratory tests. This chapter aims to empower internists to improve their medical practices in pain management. It provides a scientific background that covers nociception and how sensory processing occurs at multiple levels in the body. Clinical assessment is detailed, as well as diagnostic categories that include mixed or uncertain chronic pain syndromes (back pain, fibromyalgia, postamputation pain, pain from cancer and bone) and neuropathic pain syndromes (polyneuropathy, mononeuropathy multiplex, ganglionopathy, genetic disorders, focal and regional syndromes). Treatment of chronic pain can be surgical or interventional. Pharmacologic treatment for acute and chronic nociceptive pain includes special considerations for geriatric and terminal patients. For treatment of neuropathic pain, medications are the major component. One tables lists iatrogenic nerve injuries that can cause posttraumatic neuralgia and complex regional pain syndrome. Other tables detail stepwise pharmacologic management of neuropathic pain and cite recommendations on opioid use from the Centers for Disease Control and Prevention. One figure illustrates how pain transducers monitor and influence tissue conditions. Other figures show sensory processing in the spinal cord dorsal horn, physical findings in the feet of patients with bilateral foot pain from small-fiber polyneuropathy, illustrate how examination can identify specific nerve injuries causing chronic pain, and provide classification of chronic pain syndromes. This chapter contains 82 references.

Effects of ralfinamide in models of nerve injury and chemotherapy-induced neuropathic pain

Neuropathic pain is among the most common and difficult-to-treat types of chronic pain and is associated with sodium channel malfunction. The sodium channel blocker ralfinamide has exhibited potent analgesic effects in several preclinical pain models and in patients with mixed neuropathic pain syndromes (Phase II trials), but it failed to ameliorate neuropathic low back pain in Phase III trials. It is unclear whether ralfinamide is effective against neuropathic pain induced by specified etiologies. In the present study, the antinociceptive effects of ralfinamide in neuropathic pain models induced by spared nerve injury and chemotherapy were compared in a gabapentin-controlled manner. The effects of ralfinamide on physiological pain were evaluated in mechanical withdrawal, hot plate, and acetic acid writhing tests. We also investigated the effects of ralfinamide on cardiovascular function and locomotor activity. Oral ralfinamide dose-dependently alleviated spared nerve injury-induced allodynia in rats and mice. Ralfinamide increased mechanical withdrawal thresholds in oxaliplatin-induced and paclitaxel-induced neuropathic pain. Ralfinamide did not affect physiological pain, locomotion, or cardiovascular function. Together, ralfinamide attenuated mechanical allodynia in all the neuropathic pain models tested, with subtle differences in efficacy. The effect of ralfinamide is comparable to that of gabapentin, but with no interference in basal mechanical sensitivity. The present study supports the effectiveness of selective sodium channel blockade as an analgesic strategy, as well as the development of compounds similar to ralfinamide.

Challenges in using Symptoms Based Screening Tools while Assessing Neuropathic Pain Component in Patients with Chronic Low Back Pain.

Challenges in using Symptoms Based Screening Tools while Assessing Neuropathic Pain Component in Patients with Chronic Low Back Pain.

Pain Syndromes Other Than Headache

Pain is experienced within a complex biologic, emotional, psychological, and social context that may defy physical examination, diagnostic procedures, and laboratory tests. This chapter aims to empower internists to improve their medical practices in pain management. It provides a scientific background that covers nociception and how sensory processing occurs at multiple levels in the body. Clinical assessment is detailed, as well as diagnostic categories that include mixed or uncertain chronic pain syndromes (back pain, fibromyalgia, postamputation pain, pain from cancer and bone) and neuropathic pain syndromes (polyneuropathy, mononeuropathy multiplex, ganglionopathy, genetic disorders, focal and regional syndromes). Treatment of chronic pain can be surgical or interventional. Pharmacologic treatment for acute and chronic nociceptive pain includes special considerations for geriatric and terminal patients. For treatment of neuropathic pain, medications are the major component. One tables lists iatrogenic nerve injuries that can cause posttraumatic neuralgia and complex regional pain syndrome. Other tables detail stepwise pharmacologic management of neuropathic pain and cite recommendations on opioid use from the Centers for Disease Control and Prevention. One figure illustrates how pain transducers monitor and influence tissue conditions. Other figures show sensory processing in the spinal cord dorsal horn, physical findings in the feet of patients with bilateral foot pain from small-fiber polyneuropathy, illustrate how examination can identify specific nerve injuries causing chronic pain, and provide classification of chronic pain syndromes. This chapter contains 82 references.

Pain Syndromes Other Than Headache

Pain is experienced within a complex biologic, emotional, psychological, and social context that may defy physical examination, diagnostic procedures, and laboratory tests. This chapter aims to empower internists to improve their medical practices in pain management. It provides a scientific background that covers nociception and how sensory processing occurs at multiple levels in the body. Clinical assessment is detailed, as well as diagnostic categories that include mixed or uncertain chronic pain syndromes (back pain, fibromyalgia, postamputation pain, pain from cancer and bone) and neuropathic pain syndromes (polyneuropathy, mononeuropathy multiplex, ganglionopathy, genetic disorders, focal and regional syndromes). Treatment of chronic pain can be surgical or interventional. Pharmacologic treatment for acute and chronic nociceptive pain includes special considerations for geriatric and terminal patients. For treatment of neuropathic pain, medications are the major component. One tables lists iatrogenic nerve injuries that can cause posttraumatic neuralgia and complex regional pain syndrome. Other tables detail stepwise pharmacologic management of neuropathic pain and cite recommendations on opioid use from the Centers for Disease Control and Prevention. One figure illustrates how pain transducers monitor and influence tissue conditions. Other figures show sensory processing in the spinal cord dorsal horn, physical findings in the feet of patients with bilateral foot pain from small-fiber polyneuropathy, illustrate how examination can identify specific nerve injuries causing chronic pain, and provide classification of chronic pain syndromes. This chapter contains 82 references.

Mixed Cryoglobulinemia and HCV: An Overview

Chronic Hepatitis C Virus (HCV) is a worldwide public health problem affecting over 170 million people, or about 3% of the world’s population. In Egypt, the situation is quite worse, with the overall prevalence (percentage of people) positive for antibody to HCV being 14.7% [1]. HCV predominantly affects the liver but it can also produce a number of extra hepatic manifestations. It has been reported that 74% of patients with hepatitis C have at least one extra hepatic manifestation, the most common conditions including essential mixed cryoglobulinemia (40%), arthralgia or joint pain (23%), paresthesia (17%), myalgia (15%), pruritus (15%), and sicca syndrome (11%) [2]. Cryoglobulinemia is a haematological disorder caused by abnormal proteins deposited in small and medium-sized blood vessels called cryoglobulins aggregated together with cooling of the blood and then dissolve again when rewarmed. These can lead to vascular insufficiency in the affected organs(eg. Jointsm types II and III have rheumatoid factor whereas it is absent in type I (Table 1). The most common and severe form Is Mixed Cryoglobulinemia (MC), a systemic vacuities involving small and medium-sized arteries and veins. MC is characterized by the deposition of immune complexes containing mainly rheumatoid factor, IgG, HCV RNA, and complement on endothelial surfaces, resulting in vascular inflammation, albeit through poorly understood mechanisms. Moreover, HCV can trigger impairment in lymph proliferation with cryoglobulin production [3]. A triad of purpura, arthralgia, and asthenia is the most characteristic clinical features of this syndrome, involvement of the renal & peripheral nervous systems commonly occur [4]. In a large prospective study of 1614 patients chronically infected with HCV, mixed cryoglobulinemia was the predominant extra-hepatic biologic manifestation, identified in 40% of patients. Using multivariate analysis, four independent factors were found to be significantly associated with the presence of cryoglobulins: female sex, alcohol consumption more than 50 g/d, HCV genotype II or III, and extensive liver fibrosis. Cryoglobulin-positive patients were examined for arthralgias, arterial hypertension, purpura, and systemic vasculitis. Considering the high frequency of positive cryoglobulins in patients with HCV, severely symptomatic mixed cryoglobulinemia with vasculitis was rare, noted in only 2 to 3% of cryoglobulin-positive patients [3,5].

Diagnostics of pain syndromes of the lumbar spinal region by applied kinesiology methods

Differential diagnostics of pain syndromes of the lumbar spinal region by means of applied kinesiology methods was made. Clinical groups of patient are analyzed, the main causes of the mechanisms of formation vertebrogenic, visceral and mixed pain syndromes of the lumbar spinal region are found. On examples of patients with chronic pain in the lumbar spinal region the application of applied kinesiology methods in the diagnostic and therapeutic process has been found to be reasonable.

Assessment of the feasibility of high-concentration capsaicin patches in the pain unit of a tertiary hospital for a population of mixed refractory peripheral neuropathic pain syndromes in non-diabetic patients.

BackgroundHigh-concentration-capsaicin-patches (Qutenza®) have been put on the market as a treatment for peripheral neuropathic pain. A minimum infrastructure and a determinate skill set for its application are required. Our aim was to assess the feasibility of treatment with high-concentration-capsaicin-patches in clinical practice in a variety of refractory peripheral neuropathic pain syndromes in non-diabetic patients.MethodsObservational, prospective, single-center study of patients attended to in the Pain Unit of a tertiary hospital, ≥18 year-old non-responders to multimodal analgesia of both genders. The feasibility for the application of capsaicin patch in clinical practice was evaluated by means of the number of patients controlled per day when this one was applied and by means of the times used for patch application.ResultsBetween October 2010 and September 2011, 20 consecutive non-diabetic patients (7 males, 13 females) with different diagnoses of refractory peripheral neuropathic pain syndromes, with a median (range) age of 60 (33–88) years-old were treated with a single patch application. The median (range) number of patients monitored per day was not modified when the capsaicin patch was applied [27 (26–29)] in comparison with it was not applied [28 (26–30)]. The median (range) total time to determine and mark the painful area was 9 (6–15) minutes and of patch application was 60 (58–65) minutes. No important adverse reactions were observed.ConclusionHigh-concentration-capsaicin-patch treatment was feasible in our unit for the treatment of a population with refractory peripheral neuropathic pain. The routine of our unit was not affected by its use.

Current perspectives on intrathecal drug delivery.

Advances in intrathecal analgesia and intrathecal drug delivery systems have allowed for a range of medications to be used in the control of pain and spasticity. This technique allows for reduced medication doses that can decrease the side effects typically associated with oral or parenteral drug delivery. Recent expert panel consensus guidelines have provided care paths in the treatment of nociceptive, neuropathic, and mixed pain syndromes. While the data for pain relief, adverse effect reduction, and cost-effectiveness with cancer pain control are compelling, the evidence is less clear for noncancer pain, other than spasticity. Physicians should be aware of mechanical, pharmacological, surgical, and patient-specific complications, including possible granuloma formation. Newer intrathecal drug delivery systems may allow for better safety and quality of life outcomes.

Cervicalgia, cervicocranialgia, and cervicogenic headache

Pain syndromes in the neck and head regions are one of the most difficult conditions to be interpreted in clinical practice. Craniocervical anatomical and physiological features are a basis for development of mixed pain syndromes showing as a polymorphic clinical picture in the presence of not only painful, but also tonic muscle, autonomic, postural, vestibular, and other disorders. The current concept of cervicocranialgia is based on the views and convergence between cranial (trigeminal) and upper cervical afferents, as supported by clinical and experimental data. These mechanisms are responsible for referred pain phenomena that are so characteristic of myofascial pain syndromes in the neck, head, and face. Myofascial pain may both be independent and occur in other types of primary headaches, specifically in migraine and tension headache. In these cases, the clinical symptomatology takes the features that are highly characteristic of myofascial pain: referred pain with a typical pattern of its spread, as well as trigger points and pain associated with postural loads and other physical factors. These peculiarities should be kept in mind when diagnosing pain syndromes in the craniocervical region. Current approaches to managing patients with cervicocranialgias encompass relief of pain and tonic muscle disorders and compensation for postural disturbances. For this, it is customary to use pharmacotherapy with antidepressants, nonsteroidal anti-inflammatory drugs, and myorelaxants. Effective analgesia in these patients still remains an unsolved problem. Analysis of clinical trials can identify the most effective analgesic and safe agents for pharmacotherapy. The phenomena of myofascial pain determine the expediency of using myorelaxants that exert an intrinsic analgesic effect and reduce tonic muscle phenomena.

Chronic pain patients' treatment preferences: a discrete-choice experiment.

The objective of this study was to identify, document, and weight attributes of a pain medication that are relevant from the perspective of patients with chronic pain. Within the sub-population of patients suffering from "chronic neuropathic pain", three groups were analyzed in depth: patients with neuropathic back pain, patients with painful diabetic polyneuropathy, and patients suffering from pain due to post-herpetic neuralgia. The central question was: "On which features do patients base their assessment of pain medications and which features are most useful in the process of evaluating and selecting possible therapies?" A detailed literature review, focus groups with patients, and face-to-face interviews with widely recognized experts for pain treatment were conducted to identify relevant treatment attributes of a pain medication. A pre-test was conducted to verify the structure of relevant and dominant attributes using factor analyses by evaluating the most frequently mentioned representatives of each factor. The Discrete-Choice Experiment (DCE) used a survey based on self-reported patient data including socio-demographics and specific parameters concerning pain treatment. Furthermore, the neuropathic pain component was determined in all patients based on their scoring in the painDETECT(®) questionnaire. For statistical data analysis of the DCE, a random effect logit model was used and coefficients were presented. A total of 1,324 German patients participated in the survey, of whom 44% suffered from neuropathic back pain (including mixed pain syndrome), 10% complained about diabetic polyneuropathy, and 4% reported pain due to post-herpetic neuralgia. A total of 36 single quality aspects of pain treatment, detected in the qualitative survey, were grouped in 7 dimensions by factor analysis. These 7 dimensions were used as attributes for the DCE. The DCE model resulted in the following ranking of relevant attributes for treatment decision: "no character change", "less nausea and vomiting", "pain reduction" (coefficient: >0.9 for all attributes, "high impact"), "rapid effect", "low risk of addiction" (coefficient ~0.5, "middle impact"), "applicability with comorbidity" (coefficient ~0.3), and "improvement of quality of sleep" (coefficient~0.25). All attributes were highly significant (p<0.001). The results were intended to enable early selection of an individualized pain medication. The results of the study showed that DCE is an appropriate means for the identification of patient preferences when being treated with specific pain medications. Due to the fact that pain perception is subjective in nature, the identification of patients´ preferences will enable therapists to better develop and implement patient-oriented treatment of chronic pain. It is therefore essential to improve the therapists´ understanding of patient preferences in order to make decisions concerning pain treatment. DCE and direct assessment should become valid instruments to elicit treatment preferences in chronic pain.

Sympathetic Nervous System activity – a new concept of the complicated etiology of low back pain radiates distally at the extremities

Varied and complicated etiology of low back pain radiates distally at the extremities is still causing disagreement and controversies around the issue of its diagnosis and treatment. New research data demonstrated that almost one in five persons with back pain experience symptoms indicative of neuropathic pain component. The neuropathic involvement is not completely understood, and different mechanisms are thought to play important role. A combination of nociceptive and neuropathic pain-generating mechanism is thought to be involved, which established the term mixed pain syndrome. In the pathomechanism of neuropathic pain the lesion, trauma or overloading of the disc is thought to be a primary source of the neuropathic pain but the concept of neuropathic component of pain is more probable for chronic stage than acute. Assessment of neuropathic pain involves a systematic approach which includes a series steps; past and present history, detailed description of pain distribution, quality, pain intensity and neurological examination with emphasis on sensory testing. The sensory examinations need often to be supply neurophysiological testing and quantitate sensory testing. Some groups of the drugs are thought to be useful e.g. tricyclic antidepressant, sodium channel blockers (e.g. carbamazepine), gabapentin, opioids, NMDA (N-methyl-D-aspartate) receptor blockers and others for neuropathic pain treatment. The use of specific kind of the drugs depends on the symptoms and examinations findings.