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Almost 10% of the world's population is affected by alcohol use disorder (AUD). The combination between psychosocial intervention and pharmacological treatment seems to be the most effective approach for patients affected by AUD. Among effective drugs useful in the treatment of AUD, GABAB-ergic medications have been tested with encouraging results (i.e. sodium oxybate, baclofen, gabapentin, pregabalin and tiagabine). The present review will summarize available data on these medications.
This study demonstrates that the pretreatment with MAB, given orally (8.4 to 83.8 μmol/kg), inhibited carrageenan- and complete Freund adjuvant-induced mechanical hypersensitivity. When administered after the induction of hypersensitivity, MAB also reduced the mechanical hypersensitivity in the ipsilateral and in the contralateral hindpaws of mice injected with complete Freund adjuvant, interfering with a signaling cascade already established. MAB reversed the hypersensitivity (mechanical and thermal) of operated animals, with similar results to those observed with gabapentin. MAB activity was evident when administered either systemically (PO or IV) or intrathecally, suggesting interference in the central pathways of pain control. Furthermore, MAB seems to present an antiinflammatory effect evidenced by the interference in both the neutrophil migration and in the increase of interleukin-1β levels after carrageenan injection. Of note, MAB treatment did not interfere with mechanical or thermal sensitivity in healthy mice, a frequent characteristic of commonly used analgesics, such as morphine or gabapentin. Side effects including interference in locomotor activity, motor performance, and body temperature in animals treated with MAB were absent.
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This study underpins the poor pharmacotherapeutic prognosis of PTTN. The results support findings on neuropathic pain in other sites and point to the need for further research and reexamination of current PTTN treatment protocols.
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The calcium channel alpha2delta-1 subunit is a structural subunit important for functional calcium channel assembly. In vitro studies have shown that this subunit is the binding site for gabapentin, an anticonvulsant that exerts antihyperalgesic effects by unknown mechanisms. Increased expression of this subunit in the spinal cord and dorsal root ganglia (DRG) has been suggested to play a role in enhanced nociceptive responses of spinal nerve-injured rats to innocuous mechanical stimulation (allodynia). To investigate whether a common mechanism underlies allodynic states derived from different etiologies, and if so, whether similar alpha2delta-1 subunit up-regulation correlates with these allodynic states, we compared DRG and spinal cord alpha2delta-1 subunit levels and gabapentin sensitivity in allodynic rats with mechanical nerve injuries (sciatic nerve chronic constriction injury, spinal nerve transection, or ligation), a metabolic disorder (diabetes), or chemical neuropathy (vincristine neurotoxicity). Our data indicated that even though allodynia occurred in all types of nerve injury investigated, DRG and/or spinal cord alpha2delta-1 subunit up-regulation and gabapentin sensitivity only coexisted in the mechanical and diabetic neuropathies. Thus, induction of the alpha2delta-1 subunit in the DRG and spinal cord is likely regulated by factors that are specific for individual neuropathies and may contribute to gabapentin-sensitive allodynia. However, the calcium channel alpha2delta-1 subunit is not the sole molecular change that uniformly characterizes the neuropathic pain states.
Subjects randomized to gabapentin demonstrated improvement in the sleep quality factor score, compared to placebo-treated subjects, at 4 and 12 weeks (p < 0.03). There was also gabapentin-associated improvement in the global PSQI score (p = 0.004) and the sleep efficiency factor score (p = 0.05) at 4 weeks. There was no significant effect of gabapentin on the daily disturbance factor score.
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This study used administrative claims databases for commercially-insured individuals aged 18-64 years to examine factors associated with treatment among DPNP patients who initiated duloxetine versus tricyclic antidepressants (TCAs), venlafaxine, gabapentin, pregabalin, or opioids between 7/1/2005 and 12/31/2007. Treatment initiation was defined as no pill coverage of the same medication over the previous 90 days. Multiple logistic regression models were estimated to assess factors associated with initiating duloxetine versus each of the other DPNP therapies.
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The mean age at onset was 48.5 years (SD: 19.8, range: 23-83). All the patients complained of strictly unilateral pain paroxysms starting at parietal (n = 5), occipital (n = 4), or parieto-occipital locations (n = 1), and immediately spreading forward through a linear pathway toward the ipsilateral forehead (n = 3) or the ipsilateral eye (n = 7), the complete sequence lasting 1-10 seconds. No trigger was identified in any of our patients, while 5 of them suffered mild pain in the stemming area between the paroxysms. Three patients had ipsilateral lacrimation, and 2 had conjunctival injection at the end of the attacks. The frequency ranged from 1 attack per week to multiple attacks per day. Neuroimaging and laboratory tests were consistently normal. Interictal pain was responsive to acetaminophen. In 3 cases a preventive was considered in order to avoid the paroxysms. Gabapentin led to significant improvement in 2 cases. The third patient did not obtain any benefit from gabapentin or amitriptyline, but improved slightly with lamotrigine.
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UP is an unpleasant itching sensation that affects approximately 30% of patients on hemodialysis (HD). The current mainstays of therapy include antihistamines and topical therapies, although many patients remain symptomatic despite these treatments. Alternative therapeutic approaches, including topical, oral, and intravenous drugs; dialysis modifications; homeopathic therapies; and physical treatments have been used, but few evidence-based studies exist to support their utility. Gabapentin has been evaluated for the treatment of UP in 2 small, randomized, placebo-controlled studies, 1 pilot evaluation, and 1 index case. Gabapentin has demonstrated efficacy in the treatment of multiple types of itch and shows promise in treating patients with UP who are unresponsive to standard therapies. All of the controlled studies consisted of 4 weeks of active treatment, and no patients discontinued gabapentin due to adverse events. The most common adverse events noted in these trials were consistent with gabapentin's safety profile (dizziness, somnolence, fatigue, nausea).
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Fibromyalgia affects an estimated 2% of the general U.S. population, and its incidence is sevenfold higher among women. The diagnostic characteristics of fibromyalgia are chronic widespread pain, thought to arise from abnormalities of ascending pain and descending inhibitory sensory pathways, and allodynia on palpation of specific tender points. Three medications available in the United States are labeled for treatment of fibromyalgia-related symptoms: the serotonin- and norepinephrine-reuptake inhibitors duloxetine and milnacipran and the α(2)-δ ligand pregabalin. Evidence from clinical trials indicates that all three drugs can have a significant impact on fibromyalgia-related pain; duloxetine and pregabalin have been demonstrated to reduce sleep disturbances and improve quality of life (the former also has been shown to improve mood), while milnacipran can offer significant benefits in reducing fatigue. A growing body of evidence suggests that the best treatment approach may involve the use of one or more agents whose mechanisms of action are aligned with patient-specific clusters of symptoms. Several other agents have been used for fibromyalgia, with mixed results, including tricyclic antidepressants, selective serotonin-reuptake inhibitors, opioids, and gabapentin. Given the limitations of the evidence from clinical trials to date, controlled trials directly comparing different agents are needed to better delineate adverse-event risks, cost considerations, and optimal management approaches.
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Spinal-cord injury (SCI) is a leading cause of neuropathic pain (NP). Current pharmaceutical treatments for NP in SCI patients are not effective. Two promising options are gabapentin (GP) and pregabalin (PB). Their predominant mechanism of action is believed to be the inhibition of calcium currents, leading in turn to reduced neurotransmitter release and attenuation of postsynaptic excitability. This could explain much of their efficacy in the treatment of both seizure disorders and pain syndromes. However, evidence for their efficacy in attenuating NP of SCI is still controversial.
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No studies were found in which this information was available for OXC, PGB, TGB or ZNS. The number of patients who achieved seizure freedom for 6 months was reported in four studies each for GBP and TPM, five studies for LTG, and eight studies for LEV. The best efficacy profile using this end point was found for LEV, followed by TPM, LTG, and GBP. Twenty-two studies reported the number of patients withdrawing due to adverse effects. LEV was the best-tolerated AED, a little ahead of LTG, and significantly better than GBP or TPM . TPM was by far the least well-tolerated drug. Information concerning patients continuing treatment after 1 year was reported in two GBP studies, two TPM studies, six LEV studies and five LTG studies. GBP had a very low retention rate (between 20% and 25% of patients continued the drug), while TPM and LTG had a retention rate of 40-60% and LEV had a retention rate of 60-75%.