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)

Tension-type headache typically causes pain that radiates in a band-like fashion bilaterally from the forehead to the occiput. Pain often radiates to the neck muscles and is described as tightness, pressure, or dull ache. Migraine-type features (unilateral, throbbing pain, nausea, photophobia) are not present All patients with frequent or severe headaches need careful evaluation to exclude any occult serious condition that may be causing the headache. Neuroimaging is not needed in patients who have no worrisome findings on examination. Treatment of tension-type headache typically involves the use of over-the-counter analgesics. Use of pain relievers more than twice weekly places patients at risk for progression to chronic daily headache. Sedating antihistamines or antiemetics can potentiate the pain-relieving effects of standard analgesics. Analgesics combined with butalbital or opiates are often useful for tension-type pain but have an increased risk of causing chronic daily headache. Amitriptyline is the most widely researched prophylactic agent for frequent headaches. No large trials with rigorous methodologies have been conducted for most non-medication therapies. Among the commonly employed modalities are biofeedback, relaxation training, self-hypnosis, and cognitive therapy.
 ...
PMID:Tension-type headache. 1232 65

(1) Pain generally disappears when herpes zoster lesions have healed, but the risk of postherpetic neuralgia, though it is low, increases with age. (2) Antivirals prescribed during the acute phase do not reduce the risk of postherpetic neuralgia, but they do reduce its duration. (3) Common non specific analgesics such as paracetamol seem inadequate against postherpetic neuralgia. Amitriptyline and desipramine, despite their limited efficacy, are the reference. Gabapentin, although somewhat less effective, is a possible second line option. It is unclear how long treatment should last.
 ...
PMID:Treatment of postherpetic neuralgia: tricyclic antidepressants still the reference. 1247

The local, peripheral administration of antidepressants and excitatory amino acid receptor antagonists can cause analgesia in a number of conditions. The present study examined the effects of combinations of dextromethorphan and ketamine, two clinically used N-methyl-D-aspartate (NMDA) receptor antagonists, with amitriptyline on formalin-evoked behaviors and paw edema. Pretreatment with amitriptyline or dextromethorphan (10-300 nmol) resulted in suppression of flinching behaviors induced by 2.5% formalin, but ketamine had no intrinsic effect. Combination of an inactive dose of dextromethorphan with amitriptyline, and vice versa, resulted in an increase of analgesia so that previously inactive doses now caused significant analgesia. Combinations of multiple doses of ketamine with amitriptyline did not modify the response to amitriptyline. Both dextromethorphan and ketamine increased the paw edema induced by formalin, and this was blocked by low doses of amitriptyline. In the absence of formalin, amitriptyline (1-100 nmol) caused a dose-related suppression of the paw edema produced by dextromethorphan and ketamine. Amitriptyline also blocked paw edema produced by 5-hydroxytryptamine and compound 48/80. Each of the drugs used in this study exerts multiple pharmacological effects. Increased analgesia by drug combinations (amitriptyline/dextromethorphan) could show the involvement of a number of these mechanisms (e.g. NMDA receptor blockade, blockage of sodium channels, blockage of biogenic amine receptors), while a lack of intensification (amitriptyline/ketamine) could reflect occluded actions due to expression of similar actions by the other drug. Paw edema induced by dextromethorphan and ketamine involves inhibition of biogenic amine reuptake, and the ability of amitriptyline to block biogenic amine receptors likely accounts for its inhibiton of these actions. Combinations of these particular agents could represent a method for augmented analgesia and minimization of local adverse reactions.
Pain 2003 Mar
PMID:Peripheral interactions between dextromethorphan, ketamine and amitriptyline on formalin-evoked behaviors and paw edema in rats. 1262 Jun 9

The complete Freund's adjuvant (CFA)-induced arthritic rat model has extensively served as a laboratory model in the study of arthritic pain. However, the time courses of allodynia and hyperalgesia and the efficacies of different analgesics have not fully been analyzed in this model. Mechanical allodynia, thermal and joint hyperalgesia, and other disease development parameters (body weight, mobility, paw volume, and joint stiffness) were measured on postinoculation days (PIDs) 0 to 28 in rats. Acute analgesic efficacies of drugs were evaluated on PID 9 when degrees of allodynia, hyperalgesia, and joint stiffness in the ipsilateral paw reached almost the maximum, although those in the contralateral paw changed only slightly. In the ipsilateral paw, thermal hyperalgesia reached the maximum on PID 1, whereas mechanical allodynia and joint hyperalgesia progressively developed during the first 7 or 8 days, being tuned in to arthritis development. In the contralateral paw, thermal hyperalgesia never occurred, whereas mechanical allodynia and joint hyperalgesia developed after PID 11. Morphine and tramadol had full efficacies for all the pain parameters tested at sedation-inducing doses. Indomethacin and diclofenac significantly but partially improved thermal and joint hyperalgesia. Amitriptyline significantly reduced thermal and joint hyperalgesia only at sedation-inducing dose. Acetaminophen, carbamazepine, and gabapentin had, at the most, very small efficacies. In conclusion, the present study provided integrated information about the time course of pain and other disease development parameters in the CFA-induced arthritic rats, and clarified acute efficacies of different categories of analgesics for the allodynia and hyperalgesia.
 ...
PMID:Allodynia and hyperalgesia in adjuvant-induced arthritic rats: time course of progression and efficacy of analgesics. 1273 Feb 75

Amitriptyline, nortriptyline, imipramine, doxepin, desipramine, protriptyline, trimipramine, and maprotiline are tricyclic antidepressants (TCAs) used orally in treating major depressive disorders. Recent studies showed that amitriptyline is more potent in blocking the sciatic nerve functions in vivo by local injection than bupivacaine, a long-acting local anesthetic. We therefore tested whether various TCAs could likewise act as local anesthetics in vivo after single injection via the rat sciatic notch. The duration of complete sciatic nerve blockade by TCAs and the time to reach full recovery were measured with neurobehavioral assays and compared with results from bupivacaine. Amitriptyline, doxepin, and imipramine at 5mM elicited a longer complete sciatic nerve blockade than did bupivacaine at 15.4mM (0.5%), whereas trimipramine and desipramine at 5mM produced a shorter blockade. In contrast, nortriptyline, protriptyline, and maprotiline failed to elicit complete sciatic nerve blockade. Thus, TCAs have very different efficacy as local anesthetics in vivo. The duration of rat sciatic nerve blockade in vivo by TCAs is not well correlated with the 50% inhibitory concentration (IC(50)) of TCAs in blocking human cardiac Nav1.5 Na(+) channels expressed in human embryonic kidney cells. With this in vitro expression system, TCAs appear more potent than bupivacaine as Na(+) channel blockers in Nav1.5 Na(+) channels. We suggest that the ability of TCAs to pass through various membrane barriers within peripheral nerve trunks is crucial to their local anesthetic efficacy in vivo. TCAs with a tertiary amine appear more effective in penetrating these membrane barriers than TCAs with a secondary amine.
Pain 2003 May
PMID:Tricyclic antidepressants as long-acting local anesthetics. 1274 58

The development of neuropathic pain following stroke is not uncommon. The consequences include significant disabilities and depression. Treatment can often be difficult and responses unsatisfactory. We report a patient with severe central post-stroke pain (CPSP) of the right leg benefiting from a combination of Western multidisciplinary therapies AND acupuncture. A literature search has revealed that relatively few studies have been done on the management of CPSP, compared with other types of neuropathic pain. Amitriptyline and carbamazepine were found to produce positive effects on post-stroke pain in one small study; lamotrigine and gabapentin are two newer drugs which appear promising. To the best of our knowledge, the use of acupuncture for the treatment of CPSP has not been previously reported.
 ...
PMID:An East-West approach to the management of central post-stroke pain. 1276 58

The effects of chronic, low-dose amitriptyline on serotonin (5-HT) synthesis rate were measured in rat brain using autoradiography and the trapping of alpha-[14C]-methyl-L-tryptophan (alpha-[14C]-MTrp). Rats received amitriptyline (2 mg/kg per day) or saline via intraperitoneal osmotic minipumps for 21 days. Amitriptyline had no effect on any physiological parameters measured, or on free or total plasma tryptophan levels. However, amitriptyline exerted selective decreases of 15% and 17% (P < 0.001) in serotonin synthesis rates in the dorsal and median raphe nuclei, respectively. There was no reduction in any of the projection areas studied, including the cerebral cortex, hippocampus, thalamus, hypothalamus or striatum. The data suggest that chronic low doses of amitriptyline can lead to sustained 5-HT re-uptake inhibition selectively in the raphe nuclei, an effect compatible with tonic activation of 5-HT(1A) autoreceptors and inhibition of 5-HT synthesis. The failure of chronic amitriptyline treatment to affect 5-HT synthesis rate in the projection areas may ensure an adequate regulation of pain pathways implicated in migraine headache, an effect possibly related to amitriptyline anti-migraine efficacy.
 ...
PMID:Selective decrease in serotonin synthesis rate in rat brainstem raphe nuclei following chronic administration of low doses of amitriptyline: an effect compatible with an anti-migraine effect. 1278 Jul 67

Temporomandibular disorder (TMD) is characterized by a combination of symptoms affecting the temporomandibular joint and/or chewing muscles. The two most common clinical TMD symptoms are pain and dysfunction. Pain is usually caused by dysfunction, and emergency therapy has focused on controlling it. Recent investigations into TMD have led to the recommendation of antidepressants as a supporting treatment against constant neuralgic pain. The aim of this double-blind study was to verify the efficiency of antidepressants (amitriptyline) as a support in the treatment of chronic TMD pain. Twelve female volunteers presenting chronic TMD pain were divided into two groups and treated for 14 days: Group 1 with 25 mg/day of amitriptyline and Group 2 with a placebo. The intensity of pain and discomfort was evaluated daily, using a visual analog scale (VAS), over a period of seven days preceding the treatment (baseline), during the 14-day treatment, and for seven days after the treatment. The results revealed a significant reduction of pain and discomfort in Group 1 (75%) compared to Group 2 (28%) during the three weeks beginning at baseline (p < 0.01). Amitriptyline proved to be an efficient alternative treatment for chronic pain in TMD patients.
 ...
PMID:Clinical evaluation of amitriptyline for the control of chronic pain caused by temporomandibular joint disorders. 1288 79

The inoculation of mice with herpes simplex virus type-1 (HSV-1) causes herpes zoster-like skin lesions and pain-related responses (tactile allodynia and mechanical hyperalgesia) from day 5 after inoculation. Skin lesions completely heal by day 15 after inoculation, but about half of mice with acute herpetic pain show pain-related responses long after the lesions heal. Using this mouse model, we examined the effects of repeated administration of gabapentin and amitriptyline on the acute herpetic pain and the incidence of postherpetic pain. Gabapentin and amitriptyline were administered three times daily from day 5 to 11 after inoculation. Postherpetic pain-related responses were assessed on day 30 after inoculation. Gabapentin (10-100 mg/kg) produced the dose-dependent inhibition of acute herpetic pain-related responses. This medication produced marked reduction in the incidence of delayed postherpetic pain and the dose of 100 mg/kg produced the complete inhibition. Amitriptyline (10 mg/kg) did not affect the acute pain-related responses in the initial 3- and 2-day periods and then gradually inhibited them. This dosage produced a substantial but non-significant decrease in the incidence of postherpetic pain-related responses. Amitriptyline (1 and 3 mg/kg) was without effects on acute herpetic and postherpetic pain-related responses. The results strongly support the idea that the severity of the acute herpetic pain is a risk factor of postherpetic neuralgia. It may be worth testing the effects of gabapentin on acute herpetic pain and the incidence of postherpetic neuralgia in human subjects.
 ...
PMID:Effects of the suppression of acute herpetic pain by gabapentin and amitriptyline on the incidence of delayed postherpetic pain in mice. 1504 44

Amitriptyline is a tricyclic antidepressant, which also alleviates various pain syndromes at its therapeutic plasma concentration (0.36-0.90 microM). Accumulated evidence suggests that such efficacy may be due to block of voltage-gated Na(+) channels. The Na(+) channel alpha-subunit protein consists of four homologous domains (D1-D4), each with six transmembrane segments (S1-S6). The aims of this study were to locate the amitriptyline receptor in the Na(+) channel alpha-subunit and to compare the amitriptyline affinity in open, inactivated, and resting states of the Na(+) channel. Wild-type and mutant rat skeletal muscle alpha-subunit Na(+) channels were expressed in human embryonic kidney cells and assayed under whole-cell voltage clamp conditions. Our results indicate that the amitriptyline receptor overlaps with the local anesthetic receptor to a great extent in Na(+) channels. Residues N434 (at D1-S6), L1280 (D3-S6), and F1579 (D4-S6) may jointly form parts of the amitriptyline/local anesthetic receptor, with residue L1280 being most critical for amitriptyline binding. Open-channel block by amitriptyline was assessed in inactivation-deficient Na(+) channels and compared with the resting- and inactivated-channel block in wild-type channels. The open-channel block by amitriptyline has the highest affinity, with a 50% inhibitory concentration (IC(50)) of 0.26 microM. The inactivated-channel block by amitriptyline had a weaker affinity (0.51 microM), whereas the resting-channel displayed the weakest affinity (33 microM). We hypothesize that selective block of both persistent late openings and the inactivated state of neuronal Na(+) channel isoforms by amitriptyline also occurs at its therapeutic concentration and likely contributes to its efficacy in pain syndromes.
Pain 2004 Jul
PMID:State-dependent block of voltage-gated Na+ channels by amitriptyline via the local anesthetic receptor and its implication for neuropathic pain. 1527 64


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