Effect of lamotrigin on the development of neurogenic pain syndrome in rats

Abstract

Analgesic activity of a new anticonvulsive agent lamotrigin was studied on the model of neurogenic pain syndrome produced in rats by penicillin applied to the dorsal surface of the spinal cord and by dissection of the sciatic nerve. Lamotrigin was shown to have a profound analgesic activity. It can be used as an efficient prophylactic agent for prevention of chronic pain syndromes by suppression of the generators of pathologically enhanced excitation in the nociceptive structures which are the pathophysiological basis of the chronic pain syndromes. Key Words: lamotrigin; neurogenic pain syndromes; nociceptive neuronsNeurogenic pain syndromes appear due to damage to peripheral or central structures of the nervous system that participate in conduction of nociceptive signal [7]. They are characterized by prolonged painful seizures which cannot be arrested by conventional analgesics [2,3]. The pathophysiological basis of neurogenic pain syndromes is formation of the generators of pathologically enhanced excitation which are the aggregates of interacting hyperactive neurons producing an anomalous impulse traffic in the structures responsible for regulation of pain sensitivity. Formation of such generators results from suppression of inhibitory reactions in the central nervous system structures, which is mediated by glycin and -/-aminobutyric acid [2] and enhancement of the effect of excitatory amino acids on the nociceptive neurons via NDMA and non-NDMA receptors [7,11]. Logically, the treatment of the neurogenic pain syndromes by administration of antiepileptic drugs (carbamazepine, phenytonin, clonazepam, diazepam, etc.), which eliminate the pathological hyperactivity In this work we study the effect of a novel antiepileptic preparation lamotrigin (LT) on the development of neurogenic pain syndromes, which were elicited by application of a convulsive agent (penicillin) to the dorsal surface of the spinal cord as well as by transection of the sciatic nerve. MATERIALS AND METHODSExperiments were carried out on 73 outbred albino rats weighing 180-200 g. The ethic requirements of International Association of Study of Pain were adhered to in the experiments. The spinal pain syndrome (SPS) was produced with the help of benzyl penicillin sodium salt dissolved in 1% agar, which was applied under ether narcosis unilaterally to the dorsal surface of the lumbar segments in the spinal cord (Liv-Lv). After application of the convulsant, the wound was sutured, and the animal was placed into a glass cage for observation. The degree of SPS was evaluated by a 3-point scale [ 1].The neuropathy pain syndrome (NPS) was produced by transecting of the sciatic nerve under ether narcosis at the level of the popliteal fossa and placing

Topical Combinations to Treat Microvascular Dysfunction of Chronic Postischemia Pain

“…Furthermore, these drugs have not been combined systemically, or topically for the treatment of chronic pain. However, as single drugs, α 2 A receptor agonists, NO donors or PDE inhibitors have been used systemically to treat pain associated with angina, [28][29][30] peripheral arterial disease 31,32 and neuropathic pain, [33][34][35] indicating their usefulness in these syndromes. PA inhibitors share the vasodilator, 36 antiischemic 37 and antiplatelet aggregation 38 effects of PDE inhibitors, but their added antioxidant, 39 anticytokine, 40 antileukocyte attractant, 41 immunosuppressant, 42 and mitochondrial protective 43 effects suggest they may be more effective at relieving chronic pain.…”

Topical Combinations Aimed at Treating Microvascular Dysfunction Reduce Allodynia in Rat Models of CRPS-I and Neuropathic Pain

“…Sciatic nerve lesion has also been shown to produce microvascular disturbances in rats, including capillary stasis (decreased blood flow) and increased venular permeability 31 . Importantly, both the microvascular disturbances and signs of deafferentation pain in these rats were reduced by prophylactic systemic administration of clonidine 53 or pentoxifylline 32 . Once again, the reduced blood flow and microvascular dysfunction evidenced in rats with nerve lesions suggests that our topical treatments may be useful for neuropathic pain.…”

“…Furthermore, these agents have neither been combined systemically, nor combined in topical preparations for the treatment of chronic pain. However, α 2A receptor agonists, NO donors and PDE inhibitors have been used systemically in patients or preclinical animal models to treat pain associated with angina 13,43,66 , PAD 19,52,82 , CRPS 18,40,63,74 , neuropathic pain 32,53,60 and PDN 16,24,48,84 indicating their usefulness in these syndromes. PA inhibitors have not been used to treat chronic pain, but should be equally or more effective than PDE inhibitors since they have anti-oxidant 7,34 , anticytokine 68,76 , anti-chemotaxic 70,91 , immunosuppressant 15,23 , and mitochondrial protective 12 effects, in addition to the vasodilator 61 , anti-ischemic 90 and anti-platelet aggregation 62 effects they share with PDE inhibitors.…”