Recent Advances in the Pharmacological Management of Pain

Department of Pharmacology, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.
Drugs (Impact Factor: 4.34). 02/2007; 67(15):2121-33. DOI: 10.2165/00003495-200767150-00002
Source: PubMed


Pain is an unpleasant sensation that originates from ongoing or impending tissue damage. Management of different types of pain (acute, postoperative, inflammatory, neuropathic or cancer) is the most frequent issue encountered by clinicians and pharmacological therapy is the first line of approach for the treatment of pain. This review presents and discusses recent clinical advances regarding both the improvements in delivery of analgesic drugs and improvements in the design of analgesic molecules. The new modalities of administration of analgesics used in the clinic are reviewed, including skin patches, oral and mucosal sprays, transdermal delivery systems and intranasal administration. New insights are then presented on standard drugs used to relieve pain, such as opioids (including tramadol), NSAIDs including selective cyclo-oxygenase-2 inhibitors, paracetamol (acetaminophen), local anaesthetics and adjuvant analgesics such as antidepressants, anticonvulsants (gabapentin and pregabalin), cannabinoids, ketamine and others (e.g. nefopam). Although the understanding of pain mechanisms has improved significantly recently, much more is yet to be discovered and awaited. Broadening of our knowledge is needed to improve basic and clinical research in this field in order to better alleviate pain in millions of people.

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    • "Control of NCP usually requires higher doses of opioids then what is tolerable, thus the need for adjuvant analgesics or coanalgesics. The coanalgesic drug group include gabapentinoids (gabapentin, pregabalin), antidepressants (TCAs, duloxetine, and venlafaxine), corticosteroids, bisphosphonates, NMDA antagonists, and cannabinoids.9,92,107,108 Although it is criticized frequently, the most common approach to compare clinical trials is to compare the number-needed-to-treat and number-needed-to-harm values of drugs. "
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    ABSTRACT: Cancer pain is a serious health problem, and imposes a great burden on the lives of patients and their families. Pain can be associated with delay in treatment, denial of treatment, or failure of treatment. If the pain is not treated properly it may impair the quality of life. Neuropathic cancer pain (NCP) is one of the most complex phenomena among cancer pain syndromes. NCP may result from direct damage to nerves due to acute diagnostic/therapeutic interventions. Chronic NCP is the result of treatment complications or malignancy itself. Although the reason for pain is different in NCP and noncancer neuropathic pain, the pathophysiologic mechanisms are similar. Data regarding neuropathic pain are primarily obtained from neuropathic pain studies. Evidence pertaining to NCP is limited. NCP due to chemotherapeutic toxicity is a major problem for physicians. In the past two decades, there have been efforts to standardize NCP treatment in order to provide better medical service. Opioids are the mainstay of cancer pain treatment; however, a new group of therapeutics called coanalgesic drugs has been introduced to pain treatment. These coanalgesics include gabapentinoids (gabapentin, pregabalin), antidepressants (tricyclic antidepressants, duloxetine, and venlafaxine), corticosteroids, bisphosphonates, N-methyl-D-aspartate antagonists, and cannabinoids. Pain can be encountered throughout every step of cancer treatment, and thus all practicing oncologists must be capable of assessing pain, know the possible underlying pathophysiology, and manage it appropriately. The purpose of this review is to discuss neuropathic pain and NCP in detail, the relevance of this topic, clinical features, possible pathology, and treatments of NCP.
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    • "The classic tricyclic antidepressants have been used for the treatment of neuropathic pain due to the following 6 basic mechanisms: (1) blockage of norepinephrine, serotonin, or dopamine reuptake, (2) blockage of sodium channels, (3) antagonism of NMDA glutamate receptors, (4) sympathetic blockage, (5) effects on the visceral mechanosensitive afferent nerve fibers, and (6) effects on mood [32]. "
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    ABSTRACT: Nefopam (NFP) is a non-opioid, non-steroidal, centrally acting analgesic drug that is derivative of the non-sedative benzoxazocine, developed and known in 1960s as fenazocine. Although the mechanisms of analgesic action of NFP are not well understood, they are similar to those of triple neurotransmitter (serotonin, norepinephrine, and dopamine) reuptake inhibitors and anticonvulsants. It has been used mainly as an analgesic drug for nociceptive pain, as well as a treatment for the prevention of postoperative shivering and hiccups. Based on NFP's mechanisms of analgesic action, it is more suitable for the treatment of neuropathic pain. Intravenous administration of NFP should be given in single doses of 20 mg slowly over 15-20 min or with continuous infusion of 60-120 mg/d to minimize adverse effects, such as nausea, cold sweating, dizziness, tachycardia, or drowsiness. The usual dose of oral administration is three to six times per day totaling 90-180 mg. The ceiling effect of its analgesia is uncertain depending on the mechanism of pain relief. In conclusion, the recently discovered dual analgesic mechanisms of action, namely, a) descending pain modulation by triple neurotransmitter reuptake inhibition similar to antidepressants, and b) inhibition of long-term potentiation mediated by NMDA from the inhibition of calcium influx like gabapentinoid anticonvulsants or blockade of voltage-sensitive sodium channels like carbamazepine, enable NFP to be used as a therapeutic agent to treat neuropathic pain.
    Full-text · Article · Apr 2014 · The Korean journal of pain
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    • "Antiepileptic drugs are widely used to treat multiple non-epileptic disorders such as neuropathic and inflammatory pain, migraine, essential tremors and psychiatric disorders. These pathophysiological processes disturb neuronal excitability by modulating ion channels, receptors and intracellular signalling pathways, all of which serve as targets for pharmacological actions of different antiepileptic drugs (Guindon et al., 2007; Johannessen Landmark, 2008). Levetiracetam ([S]-a-ethyl-2-oxo-1-pyrrolidine acetamide) is a novel antiepileptic drug with a broad spectrum of anticonvulsant activity and an unusually high safety margin (De Smedt et al., 2007). "
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    ABSTRACT: Levetiracetam, a novel antiepileptic drug, has recently been shown to have antinociceptive effects in various animal models of pain. The purpose of this study was to investigate the antihyperalgesic effect of levetiracetam and its mechanism of action, by examining the involvement of GABAergic, opioidergic, 5-hydroxytryptaminergic (5-HTergic) and adrenergic systems in its effect, in a rat model of inflammatory pain. Rats were intraplantarly injected with the pro-inflammatory compound carrageenan. A paw pressure test was used to determine: (i) the effect of levetiracetam on carrageenan-induced hyperalgesia; and (ii) the effects of bicuculline (selective GABA(A) receptor antagonist), naloxone (non-selective opioid receptor antagonist), methysergide (non-selective 5-HT receptor antagonist) and yohimbine (selective alpha(2)-adrenoceptor antagonist) on the antihyperalgesic action of levetiracetam. Levetiracetam (10-200; p.o.) significantly reduced, in a dose-dependent manner, the inflammatory hyperalgesia induced by carrageenan. The antihyperalgesic effect of levetiracetam was significantly decreased after administration of bicuculline (0.5-2; i.p.), naloxone (1-3; i.p.), methysergide (0.25-1; i.p.) and yohimbine (1-3; i.p.). These results show that levetiracetam produced antihyperalgesia which is at least in part mediated by GABA(A), opioid, 5-HT and alpha(2)-adrenergic receptors, in an inflammatory model of pain. The efficacy of levetiracetam in this animal model of inflammatory pain suggests that it could be a potentially important agent for treating inflammatory pain conditions in humans.
    Full-text · Article · Sep 2010 · British Journal of Pharmacology
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