Effect of Low-Dose Amitriptyline on Autonomic Functions and Peripheral Blood Flow in Fibromyalgia: A Pilot Study

Kulshreshtha, Poorvi; Gupta, Rajiva; Yadav, Raj Kumar; Bijlani, SM Ramesh lal; Deepak, Kishore Kumar

doi:10.1111/j.1526-4637.2011.01286.x

Cited by 11 publications

(9 citation statements)

References 16 publications

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“…The most common prescribed dose (initiation and maintenance) of amitryptyline for the management of neuropathic pain ranged from 5-10 mg/day in the survey. Low dose administration of amitriptyline was also reported in the literature where it was initiated in a dose of 10 mg/day [ 21 22 23 24 ]. Suggested mechanisms for the analgesic action of low dose amitriptyline is suppression of response of peripheral C-type axons to nicotine by directly inhibiting nAChRs [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Low doses of amitriptyline, pregabalin, and gabapentin are preferred for management of neuropathic pain in India: is there a need for revisiting dosing recommendations?

et al. 2017

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BackgroundCurrent therapy for the treatment of neuropathic pain is often unsatisfactory. Considerable variation in treatment pattern still exists in spite of availability of sufficient literature from various guidelines. Recent Indian market data suggested that the utilization (sale) of drugs such as amitriptyline, pregabalin, and gabapentin was more for low-dose unit packs than that of the high-dose unit packs, raising the belief that these drugs are prescribed at a lower dose than is actually recommended in the guidelines. To test this hypothesis, a survey was conducted across speciality throughout the country to observe the prescription pattern of these drugs amongst the health care providers in India.MethodsThree hundred fifty survey forms were distributed of which 281 forms were included for analysis.ResultsIt was observed that the commonly used initiation and maintenance dose for amitriptyline, pregabalin, and gabapentin was 5–10 mg/day, 50–75 mg/day, and 100–300 mg/day, respectively. The reason to select the lower dosages was to have a balancing effect to achieve good efficacy with minimum side effects. Care-givers reported no side effects/not many side effects as a reason in 22.2%, 16.88%, and 23.86% patients with amitriptyline, pregabalin, and gabapentin, respectively. Sedation and giddiness were commonly reported with all three drugs.ConclusionsCommonly prescribed drugs for management of neuropathic pain, such as amitriptyline, pregabalin, and gabapentin are preferred at lower doses in Indian clinical settings. Acceptable efficacy and low tolerance to the standard dosage is believed to be the reason behind the prescribed dose.

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Section: Discussionmentioning

confidence: 99%

Low doses of amitriptyline, pregabalin, and gabapentin are preferred for management of neuropathic pain in India: is there a need for revisiting dosing recommendations?

et al. 2017

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“…A model has been proposed on the basis of cardiovascular autonomic changes (Kulshreshtha et al ., ) and its further neural modulation by central sensitization (Fontenele & Felix, ) to elucidate the pathogenesis of pain in patients with fibromyalgia. A hypothesis of impaired neuroeffector mechanisms seems plausible in the light of a deconditioned status and a normal sympathetic reflex arc in patients with fibromyalgia (Elam et al ., ; Kulshreshtha et al ., ,b).…”

Section: Our Model Linking Physical Deconditioning With Pain‐related mentioning

confidence: 98%

“…Amitriptyline therapy (most common conventional pharmacological treatment for FM) improves blood flow at the affected sites in patients with FM. This local action of amitriptyline corroborates fibromyalgia as a case of vascular end organ dysfunction (Kulshreshtha et al ., ) Amitriptyline, through the blockade of α 1 ‐adrenoceptors/extracellular calcium influx through voltage‐gated calcium channels, induces relaxation of the isolated mesenteric vasculature and results in the dilatation of resistance vessels in healthy subjects (Thorstrand & Lindblad, ; Vila et al ., ).…”

Section: Vascular End Organ In Patients With Fibromyalgiamentioning

confidence: 99%

“…Mechanistic modulation of the autonomic nervous system in fibromyalgia makes aerobic exercise overall most effective treatment for fibromyalgia (Wigers et al ., ). Therefore, exercise/physical activity by modulating ANS and vascular end organ substantiates our previous claim that fibromyalgia may be a vascular end organ malfunction primarily (Kulshreshtha et al ., ,b).…”

Section: Our Model Linking Physical Deconditioning With Pain‐related mentioning

confidence: 99%

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Autonomic nervous system profile in fibromyalgia patients and its modulation by exercise: a mini review

Kulshreshtha

Deepak

2012

Clin Physio Funct Imaging

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This review imparts an impressionistic tone to our current understanding of autonomic nervous system abnormalities in fibromyalgia. In the wake of symptoms present in patients with fibromyalgia (FM), autonomic dysfunction seems plausible in fibromyalgia. A popular notion is that of a relentless sympathetic hyperactivity and hyporeactivity based on heart rate variability (HRV) analyses and responses to various physiological stimuli. However, some exactly opposite findings suggesting normal/hypersympathetic reactivity in patients with fibromyalgia do exist. This heterogeneous picture along with multiple comorbidities accounts for the quantitative and qualitative differences in the degree of dysautonomia present in patients with FM. We contend that HRV changes in fibromyalgia may not actually represent increased cardiac sympathetic tone. Normal muscle sympathetic nerve activity (MSNA) and normal autonomic reactivity tests in patients with fibromyalgia suggest defective vascular end organ in fibromyalgia. Previously, we proposed a model linking deconditioning with physical inactivity resulting from widespread pain in patients with fibromyalgia. Deconditioning also modulates the autonomic nervous system (high sympathetic tone and a low parasympathetic tone). A high peripheral sympathetic tone causes regional ischaemia, which in turn results in widespread pain. Thus, vascular dysregulation and hypoperfusion in patients with FM give rise to ischaemic pain leading to physical inactivity. Microvascular abnormalities are also found in patients with FM. Therapeutic interventions (e.g. exercise) that result in vasodilatation and favourable autonomic alterations have proven to be effective. In this review, we focus on the vascular end organ in patients with fibromyalgia in particular and its modulation by exercise in general.

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“…Amitriptyline is the most common prescription drug for the management of FM. Amitriptyline has the ability to influence the autonomic nervous system [16].…”

Section: Etiologymentioning

confidence: 99%

The Role of Oxidants/Antioxidants, Mitochondrial Dysfunction, and Autophagy in Fibromyalgia

Miranda-Díaz¹,

Rodríguez-Lara²

2018

Discussions of Unusual Topics in Fibromyalgia

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Fibromyalgia (FM) is a syndrome that presents primarily in women and is characterized by generalized pain, muscle rigidity, poor quality of sleep, fatigue, cognitive dysfunction, anxiety, episodes of depression, overall sensitivity, and deterioration in the performance of day-to-day activities. In the pathophysiology of fibromyalgia neuroendocrine factors, anomalies of the autonomous nervous system, genetic characteristics, and environmental and psychosocial factors are implicated. Alterations to the cells of the central nervous system that are present in fibromyalgia are due to the toxic effects of free radicals by the high concentrations of polyunsaturated fatty acids of the membranes that are easily oxidized and the low level of protective antioxidant enzymes. In FM, defects are produced in any part of the cycle in the generation of adenosine-5′-triphosphate (ATP) by the mitochondria, which can alter energy production by the mitochondria and cause the characteristic symptoms of FM. The degradation of the mitochondria dependent on autophagy or mitophagy is an important process for maintaining the critical integrity of the mitochondria and limiting the production of reactive oxygen species (ROS). Therefore, the deregulation of autophagy and mitochondrial dysfunction could represent key aspects in the pathophysiology of FM. Management with antioxidants, vitamins, coenzyme Q10, and melatonin, in addition to the antidepressants and structural analogs of the gamma-aminobutyric acid, could modify the florid symptomatology that patients with FM have.

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Effect of Low-Dose Amitriptyline on Autonomic Functions and Peripheral Blood Flow in Fibromyalgia: A Pilot Study

Abstract: Amitriptyline therapy (10mg for 3 months) increases blood flow to the affected sites. It does not affect autonomic tone and reactivity in the patients with fibromyalgia.

Cited by 11 publications

References 16 publications

Low doses of amitriptyline, pregabalin, and gabapentin are preferred for management of neuropathic pain in India: is there a need for revisiting dosing recommendations?

Low doses of amitriptyline, pregabalin, and gabapentin are preferred for management of neuropathic pain in India: is there a need for revisiting dosing recommendations?

Autonomic nervous system profile in fibromyalgia patients and its modulation by exercise: a mini review

The Role of Oxidants/Antioxidants, Mitochondrial Dysfunction, and Autophagy in Fibromyalgia

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