Pain
-
In adult patients with migraine, transcranial magnetic stimulation (TMS) has been used to examine cortical excitability between attacks, but there have been discrepant results. No TMS study has examined cortical excitability in children or adolescents with migraine. Here, we employed TMS to study regional excitability of the occipital (phosphene threshold [PT] and suppression of visual perception) and motor (resting motor threshold and cortical silent period) cortex in ten children suffering from migraine without aura and ten healthy age-matched controls. ⋯ Motor cortex excitability was not altered in patients and did not change during the migraine cycle. These findings show that pediatric migraine without aura is associated with a systematic shift in occipital excitability preceding the migraine attack. Similar systematic fluctuations in cortical excitability might be present in adult migraineurs and may reflect either a protective mechanism or an abnormal decrease in cortical excitability that predisposes an individual to a migraine attack.
-
The aim of the present study was to examine the role of the spinal serotonergic system in the pain relieving effect of spinal cord stimulation (SCS) using a rat model of mononeuropathy. Tactile withdrawal thresholds, cold responses and heat withdrawal latencies were assessed before and after SCS. In some rats, SCS produced an attenuation of the hypersensitivity following nerve injury (SCS responding rats). ⋯ It was also found that i.t. administration of a sub-effective dose of serotonin in SCS non-responding rats markedly enhanced the pain relieving effect of SCS on tactile and cold hypersensitivity, while there was no effect on heat hyperalgesia. This enhanced effect on tactile hypersensitivity could be partially blocked by a GABA(B) receptor antagonist (CGP 35348) but not by a muscarinic M(4) receptor antagonist (Muscarinic toxin 3) administered i.t. shortly before the 5-HT injection. In conclusion, there is evidence that the spinal 5-HT system plays an important role in the mode of action of SCS involving the activation of descending serotonergic pathways that may inhibit spinal nociceptive processing partially via a GABAergic link.
-
Endometriosis is a painful disorder defined by extrauteral endometrial growths whose contribution to pain symptoms is poorly understood. Endometriosis is created in rats by autotransplanting on abdominal arteries pieces of either uterus (ENDO), which form cysts, or fat (shamENDO), which do not form cysts. ENDO, but not shamENDO induces vaginal hyperalgesia. ⋯ The increases in ENDO-induced hyperalgesia produced by the sham-cyst-removal surgery were smaller in proestrus than in other estrous stages. During the other stages (but not during proestrus), sympathetic innervation of the cysts increased. These results suggest that maintenance of ENDO-induced vaginal hyperalgesia requires continued presence of at least some ectopic endometrial tissue, and that surgical treatment that fails to remove ectopic endometrial tissue can exacerbate the hyperalgesia, possibly due in part to an increase in the cysts' sympathetic innervation.
-
Oxaliplatin is a key drug in the treatment of advanced metastatic colorectal cancer, but it causes acute peripheral neuropathy (acral paresthesias triggered by exposure to cold) and chronic neuropathy (abnormal of sensory and motor dysfunction). Oxaliplatin is metabolized to oxalate and dichloro(1,2-diaminocyclohexane)platinum (Pt(dach)Cl(2)). Although the chelating of Ca(2+) with oxalate eliminated from oxaliplatin is thought as one of the reasons for the neuropathy, there is little behavioral evidence. ⋯ The pre-administration of calcium or magnesium (0.5mmol/kg, i.v.) before oxaliplatin or oxalate prevented the cold hyperalgesia but not mechanical allodynia. However, the treatment with calcium or magnesium after the development of neuropathy could not attenuate the cold hyperalgesia or mechanical allodynia. These findings suggest the involvement of oxalate in oxaliplatin-induced cold hyperalgesia but not mechanical allodynia, and usefulness of prophylactic treatments with calcium and magnesium on the acute peripheral neuropathy.
-
The central processing of peripheral nociceptive messages is highly controlled by the activity of local inhibitory networks in the spinal cord and supraspinal centers. Recently, it has been shown that endogenous 3alpha-reduced neurosteroids (3alphaNS) exert a significant spinal antinociception by potentiating GABA(A) receptor function. Because endogenous 3alphaNS can be produced in many relay structures of the nociceptive system, we tested the potential analgesic efficacy of promoting the production of neurosteroids by using etifoxine (ETX, 50mg/kg i.p.). ⋯ Both the curative and preventive effects of ETX on pain symptoms were mediated by the production of 3alphaNS as demonstrated in animals treated with the enzymatic inhibitor provera (6-medroxyprogesterone acetate; 20mg/kg s.c.). Altogether, this study shows for the first time that promoting 3alphaNS could be a possible therapeutic strategy to treat neuropathic pain symptoms. Since ETX is already available as an anxiolytic, its use in humans, provided that its analgesic properties are confirmed, could be rapidly considered.