Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amitriptyline, which is a noradrenaline reuptake and 5-HT reuptake inhibitor, has an established role in the management of chronic tension-type headaches. In a single-blind study, patients with chronic tension-type headache were randomized to either fluoxetine 20 mg (a selective 5-HT reuptake inhibitor) or desipramine 75 mg (a selective noradrenaline reuptake inhibitor) and followed for 12 weeks to compare the effectiveness of the two drugs in improving headache, and to assess whether pain control is related to changes in depression. Patients were evaluated at weekly intervals on an analog pain-rating scale and at 4-weekly intervals on the Montgomery and Asberg Depression Rating Scale (MADRS), the MOS general health status questionnaire (SF36), the Hospital Anxiety and Depression Scale (HADS), and a side effects checklist. Eighteen patients were randomized to take fluoxetine and 19 to take desipramine. Of the 25 patients who completed the trial, 12 were on fluoxetine and 13 were on desipramine. There was no significant difference between the two groups at baseline nor in change of pain; reduction in use of analgesic medication; nor change in the HADS, MADRS, or SF36 scores at 12 weeks, but 72% of patients who completed the study improved, and this improvement almost exactly mirrored the improvement on the MADRS. The results from this trial are compatible with the notion that the beneficial effect of antidepressants in chronic tension-type headache is indirect, mediated by an effect on depression, and not more,dependent on serotonin reuptake inhibition than noradrenaline reuptake inhibition.
 ...
PMID:Antidepressant treatment of chronic tension-type headache: a comparison between fluoxetine and desipramine. 1561 68

Nociceptive responses in an animal model of peripheral nerve injury were studied. The left common sciatic nerve was exposed, tightly ligated at two locations and transected between the ligatures. A bilateral decrease in the nociceptive threshold to mechanical stimulation was observed within 3 h after the operation. The skin of the lateral dorsal part of the injured paw was hypoalgesic, while the medial dorsal paw innervated by the intact saphenous nerve and the contralateral dorsal paw exhibited hyperalgesia. Amitriptyline, an antidepressant, at 25, 50 and 100 mg/kg per day, p.o., and gabapentin, an anticonvulsant, at 30, 100 and 300 mg/kg per day, p.o., significantly inhibited the decrease in the mechanical nociceptive threshold in the injured and uninjured paws. The effects of amitriptyline at 25 and 50 mg/kg were evident at doses that did not cause neurologic deficits as assessed by the inclined screen test. Indomethacin, a cyclooxygenase inhibitor, and morphine (except at the highest dose of 30 mg/kg, s.c.) showed no analgesic effects in this model. The tail-flick latency was also significantly decreased compared with intact rats. Similar bilateral hyperalgesia was observed when axotomy was performed using silk thread instead of chromic gut. When this axotomy model was applied to mice, the nociceptive thresholds in both paws immediately showed a significant decrease in the same manner as in rats. The bilateral and systemic hyperalgesia observed in this axotomy model, which resembles the clinical features of chronic neuropathic pain, suggests the involvement of the central nervous system in the maintenance of the chronic pain state.
Pain 2005 May
PMID:Effects of amitriptyline and gabapentin on bilateral hyperalgesia observed in an animal model of unilateral axotomy. 1583 79

Amitriptyline and gabapentin are the primary treatments for painful diabetic neuropathy (PDN), and it is clear that they produce beneficial effects, but there are questions about these treatments that have not been adequately addressed. For example, although there is a growing consensus that the therapeutic effects of amitriptyline in pain patients are independent of its effects on mood, it is not clear that amitriptyline has specific and direct effects on pain. There is also a fairly broad consensus that gabapentin is safe and well tolerated, but the side-effect profile of gabapentin has not been adequately assessed in pain populations. The rat streptozotocin (STZ) model of PDN was used (a) to assess the effects of amitriptyline on objective, quantitative measures of tactile allodynia, a common type of pain in PDN patients, and (b) to assess the side effects of gabapentin using measures of motor/ambulatory and cognitive function. Amitriptyline did not attenuate STZ-induced mechanical allodynia, even after chronic administration of high doses. Gabapentin produced robust anti-allodynic effects but also produced deficits in tests of motor/ambulatory and cognitive functions. The present experiments suggest that the beneficial effects of amitriptyline in PDN may not be a result of anti-allodynic efficacy and that gabapentin produces robust anti-allodynic effects but may also produce significant motor and cognitive deficits even at or near the lowest effective doses. These findings challenge the consensus opinions about these primary treatments for PDN and suggest that their therapeutic and adverse effects should be explored further in pain patients.
 ...
PMID:Adverse effects of gabapentin and lack of anti-allodynic efficacy of amitriptyline in the streptozotocin model of painful diabetic neuropathy. 1650 4

Tension-type headache, the most common type of primary headache disorder, is reclassified in the second International Headache Society classification with clear diagnostic criteria. Chronic tension-type headache (CTTH) differs from episodic form in frequency, lack of response to most treatment strategies, more medication overuse, and more loss of quality of life. New concepts in the pathophysiology of CTTH emphasize the possible role of central nociceptive pathway sensitization in addition to peripheral myogenic factors. Mechanisms of central sensitization, even though poorly understood, may involve nitric oxide system and N-methyl-D-aspartate receptors. Future treatment modalities are likely to be based on such mechanisms. Using MRI and voxel-based morphometry, structural abnormalities have been found in patients with CTTH for the first time. Pain processing areas such as dorsal rostral and ventral pons, anterior cingulate cortex, anterior and posterior insular cortex, right posterior temporal lobe, orbitofrontal cortex, para hippocampus bilaterally, and the right cerebellum were found to have decreased gray matter in patients with CTTH compared with control subjects and patients with medication overuse headache. Amitriptyline remains the most effective preventive treatment so far. The role of botulinum toxin is not fully defined.
 ...
PMID:Tension-type headache. 1652 62

Lacosamide was tested in the streptozotocin rat model of diabetic neuropathic pain in comparison to drugs which are commonly used in the treatment of diabetic neuropathic pain, i.e. antidepressants and anticonvulsants. In diabetic rats, lacosamide attenuated cold (10, 30 mg/kg, i.p.), warm (3, 10, 30 mg/kg, i.p.) and mechanical allodynia (30 mg/kg, i.p.). Streptozotocin-induced thermal and mechanical hyperalgesia were reduced by lacosamide at doses of 10 and 30 mg/kg, i.p. Morphine (3 mg/kg) showed similar efficacy on allodynia and hyperalgesia. Amitriptyline (10 mg/kg), venlafaxine (15 mg/kg), levetiracetam (180 mg/kg) and pregabalin (100 mg/kg) exhibited significant effects on thermal allodynia and mechanical hyperalgesia. Only treatment with amitriptyline (30 mg/kg, i.p.) produced full reversal of thermal allodynia comparable to lacosamide. Lamotrigine (45 mg/kg, i.p.) had no effect on both behavioral readouts. Lacosamide's potency and efficacy in reversing pain behavior might be due to its new, yet unknown mechanism of action.
 ...
PMID:Antinociceptive efficacy of lacosamide in a rat model for painful diabetic neuropathy. 1668 22

The present study was performed to evaluate the effects of the tricyclic antidepressant amitriptyline on morphine tolerance in rats. Male Wistar rats were implanted with two intrathecal (i.t.) catheters with or without a microdialysis probe, then received a continuous i.t. infusion of saline (control) or morphine (15 microg/h) and/or amitriptyline (15 microg/h) for 5 days. The results showed that amitriptyline alone did not produce an antinociceptive effect, while morphine alone induced antinociceptive tolerance and down-regulation of spinal glutamate transporters (GLAST, GLT-1, and EAAC1) in the rat spinal cord dorsal horn. Co-administration of amitriptyline with morphine attenuated morphine tolerance and up-regulated GLAST and GLT-1 expression. On day 5, morphine challenge (10 microg/10 microl) resulted in a significant increase in levels of the excitatory amino acids (EAAs), aspartate and glutamate, in CSF dialysates in morphine-tolerant rats. Amitriptyline co-infusion not only markedly suppressed this morphine-evoked EAA release, but also preserved the antinociceptive effect of acute morphine challenge at the end of infusion. Glial cells activation and increased cytokine expression (TNFalpha, IL-1beta, and IL-6) in the rat spinal cord were induced by the 5-day morphine infusion and these neuroimmune responses were also prevented by amitriptyline co-infusion. These results show that amitriptyline not only attenuates morphine tolerance, but also preserves its antinociceptive effect. The mechanisms involved may include: (a) inhibition of pro-inflammatory cytokine expression, (b) prevention of glutamate transporter down-regulation, and even up-regulation of glial GTs GLAST and GLT-1 expression, with (c) attenuation of morphine-evoked EAA release following continuous long-term morphine infusion.
Pain 2006 Sep
PMID:Amitriptyline suppresses neuroinflammation and up-regulates glutamate transporters in morphine-tolerant rats. 1669 8

Integral to neuropathic pain is a reciprocal interaction between tumor necrosis factor-alpha (TNF) production and the alpha(2)-adrenergic receptor response, offering an attractive therapeutic target. The effects of varying levels of brain TNF on alpha(2)-adrenergic regulation of cyclic AMP (cAMP) production in the hippocampus and sciatic nerve were investigated during the development and amitriptyline treatment of chronic pain. Increased levels of TNF during the development of chronic pain transform alpha(2)-adrenergic inhibition of cAMP production in the brain to potentiation. While alpha(2)-adrenergic receptors regulate TNF production, they also affect descending noradrenergic pathways. Increases in levels of TNF in the brain deeply impact peripheral inflammation through regulating alpha(2)-adrenergic receptors, offering insight into brain-body interactions during neuropathic pain. Amitriptyline as an analgesic inhibits pain-induced increases in brain-associated TNF and transforms peripheral alpha(2)-adrenergic receptors. The dynamic equilibrium between TNF levels and alpha(2)-adrenergic functioning is uniquely altered during development and treatment of neuropathic pain. Proper manipulations of this interaction offer efficacious treatment of neuropathic pain.
 ...
PMID:Uncovering molecular elements of brain-body communication during development and treatment of neuropathic pain. 1685 92

Amitriptyline is a tricyclic antidepressant that is historically indicated and used to manage depression. More recently, due to clinical evidence demonstrating efficacy, it is often prescribed in the management of painful neuropathic disorders (PNDs). However, the amitriptyline label contains numerous preclusions (contraindications, warnings/precautions, drug interactions). Our objective was to measure the frequency of amitriptyline prescriptions in PND patients using the U.K. General Practice Research Database and assess whether any prescriptions were given to patients with preclusions listed in the product label. We identified a total of 13,546 patients (mean age 59 +/- 16.2 years; 66.7% female) who had a diagnosis of a PND and received > or =1 prescription for amitriptyline between July 1998 and June 2001. Nearly half (46.7%) of PND patients prescribed amitriptyline had > or =1 preclusion for its use; 3.5% had > or =1 contraindication; 22% had > or =1 warning/precaution; and 33% received > or =1 medication with a potential for drug interactions with amitriptyline. Preclusions were more likely in women than in men (48.3% vs. 43.4%, P < 0.0001); their incidence increased with age (42.8%, 50.4%, 55.1%, and 52.3% among those ages <65, 65-74, 75-84, and 85+ years, P < 0.0001), and the number of patients with preclusions was the highest in the phantom limb pain group (67.4%) and lowest in the atypical facial pain group (42.9%), P < 0.001. The average daily amitriptyline doses (starting: 33.6 +/- 32.4 mg; maintenance: 42.1 +/- 39.9 mg) were low compared to those used for the treatment of depression. Results indicate that, in a significant number of cases, the existence of preclusions did not prevent the prescribing of amitriptyline. Our findings raise a potential concern about the way this medication is being used. However, the clinical significance of these data is, as yet, unclear. Although, in theory, adverse outcomes may have been associated with this practice, we could not confirm this with this database analysis.
Pain Pract 2006 Dec
PMID:Prevalence of contraindicated medical conditions and use of precluded medications in patients with painful neuropathic disorders prescribed amitriptyline. 1712 7

Chronic severe pain following inguinal hernia repair is a significant post-operative problem. Its exact cause and lack of evidence-based treatment path present problems in the effective management of this surgical complication. We retrospectively reviewed the records of patients diagnosed with chronic pain following open inguinal hernia repair between November 1995 and November 2000, who were under the care of the senior author. Over the five-year period, 146 patients underwent inguinal hernia repair. 88 (60%) had suture repair (darn & modified Bassini's) and 58 (40%) underwent a Lichtenstein mesh repair. Thirteen patients (9%), (3 in suture vs. 10 in mesh group, p = 0.004) developed chronic severe pain. Examination revealed maximal tenderness over the genitofemoral nerve (GF) distribution (n = 5), over the medial end of the scar (n = 3), over the pubic tubercle (n = 1) and in the ilioinguinal nerve distribution (n = 1) No abnormality was detected on clinical examination in the cases of three patients. Treatment involved GF nerve block (n = 5), local injection of Chirocaine and Methylprednisolone acetate into the medial end of the scar (n = 3), Chirocaine and Methylprednisolone acetate into the pubic tubercle (n = 1), ilioinguinal nerve block (n = 1), re-exploration with re-suturing of the mesh (n = 1), and Amitriptyline (n = 2). At a median follow up of 45 months (range: 24-87), 10 (77%) are completely pain free; two (15.4%) had mild pain and one patient still has significant persistent pain. To conclude, chronic severe pain occurred in nine percent of patients following primary open inguinal hernia repair. The majority of patients were successfully treated by therapeutic injection into the point of maximal tenderness.
 ...
PMID:Chronic pain after hernia surgery--an informed consent issue. 1785 38

Neuropathy is common in patients receiving vinca alkaloids, platinum derivatives, or taxanes. This double-blind, randomized, placebo-controlled study assessed the efficacy of low-dose amitriptyline to relieve chemotherapy-induced symptoms in 44 patients (age 20-65 years) who had neuropathic symptoms (numbness, tingling, pain) with a severity of > or =3/10. They were treated with amitriptyline for eight weeks (10mg/day to start, then dose elevation of 10mg/week up to 50mg/day if tolerated, followed by a stable dose > or =4 weeks). The patients completed a diary twice weekly, noting the intensity of pain, numbness and tingling, global improvement, and adverse effects. Neurological examination was performed at each visit (baseline, four, and eight weeks). The patients assessed both intensity and relief of pain, and overall discomfort. They also completed the Neuropathic Pain Scale and validated measures of anxiety and depression, and quality of life (QoL). The results demonstrated that amitriptyline did not improve sensory neuropathic symptoms, although there was a trend toward global improvement and improved QoL in favor of the amitriptyline group. No statistical significance was reached, probably due to the small number of patients and too low dose of amitriptyline. Amitriptyline was well tolerated.
J Pain Symptom Manage 2008 Jan
PMID:Amitriptyline in the treatment of chemotherapy-induced neuropathic symptoms. 1798 May 50


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>