Articles: hyperalgesia.
-
The present study investigated the effects of different doses of intrathecal lidocaine on established thermal hyperalgesia and tactile allodynia in the chronic constriction injury model of neuropathic pain, defined the effective drug dose range, the duration of pain-relief effects, and the influence of this treatment on the body and tissues. Male Sprague-Dawley rats were divided into five groups and received intrathecal saline or lidocaine (2, 6.5, 15, and 35 mg/kg) 7 days after loose sciatic ligation. Respiratory depression and hemodynamic instability were found to become more severe as doses of lidocaine increased during intrathecal therapy. ⋯ These findings indicate that intrathecal lidocaine has prolonged therapeutic effects on established neuropathic pain. The balance between sympathetic and parasympathetic nervous activities could be well preserved in most cases, except for 35 mg/kg. Considering the ratio between useful effects and side effects, doses of 15 mg/kg are suitable for intrathecal injection for relief of neuropathic pain.
-
Intraplantar injection of bee venom (BV) produces persistent spontaneous nociception (PSN) and hyperalgesia, as well as obvious inflammatory swelling, in the paws of injected rats. The present study was designed to determine the peripheral roles of mitogen-activated protein kinase (MAPK) signal transduction pathways in BV-induced nociception and inflammation. We examined the effect of intraplantar injection of an ERK1/2 inhibitor, PD98059, and a p38 inhibitor, SB202190, on BV-induced PSN, mechanical hyperalgesia, and inflammatory swelling. We found that (1) pretreatment with SB202190 (0.1 to 10 microg) had no effect on BV-induced PSN, whereas pretreatment with PD98059 (0.1 to 100 microg) produced a significant and dose-dependent inhibition of BV-induced PSN; (2) pretreatment with PD98059 (0.1 to 100 microg) had no effect on BV-induced decreases in paw withdrawal mechanical threshold (PWMT), while pretreatment with SB202190 (0.1 to 10 microg) produced an obvious prevention of the BV-induced decrease in PWMT; and (3) pretreatment with PD98059 (0.1 to 100 microg) had no effect on BV-induced increase in paw volume (PV), whereas pretreatment with SB202190 (0.1 to 10 microg) produced a dose-related inhibition of BV-induced increases in PV. No contralateral drug treatments, even at the highest dose, had any effect on BV-induced PSN, PWMT or PV, ruling out the systemic effect of these drugs. These results suggest that peripheral MAPK signal transduction pathways may play differential roles in bee venom-induced nociception and inflammation. Targeting specific peripheral MAPKs might prove effective in the treatment of persistent pain and inflammation. ⋯ The present article showed that intraplantar injection of different MAPK inhibitors produced differential effects on bee venom-induced nociception and inflammation, suggesting that the peripheral MAPK signal transduction pathways have differential roles. Targeting specific peripheral MAPKs might prove effective in the treatment of persistent pain and inflammation.
-
The use of alpha-2 adrenergic agonists for analgesia is limited due to a narrow therapeutic window. Definition of the role of alpha receptor subtypes in alpha agonist mediated analgesia may identify strategies to separate the analgesic from sedative and cardiovascular effects. ⋯ Alpha-1A receptor agonist activity can counterbalance alpha-2 receptor agonist-induced analgesia. Greater alpha-2 selectivity may enhance the therapeutic window of alpha-2 agonists in the treatment of pain.
-
Annals of neurology · Feb 2009
beta(2)-adrenoceptors are critical for antidepressant treatment of neuropathic pain.
Tricyclic antidepressants (TCAs) are one of the first-line pharmacological treatments against neuropathic pain. TCAs increase the extracellular concentrations of noradrenaline and serotonin by blocking the reuptake transporters of these amines. However, the precise downstream mechanism leading to the therapeutic action remains identified. In this work, we evaluated the role of adrenergic receptors (ARs) in the action of TCAs. ⋯ Stimulation of beta(2)-AR is necessary for nortriptyline to exert its antiallodynic action against neuropathic pain. These findings provide new insight into the mechanism by which antidepressants alleviate neuropathic pain. Our results also raise the question of a potential incompatibility between beta-blockers that affect beta(2)-AR and antidepressant drugs in patients treated for neuropathic pain.
-
Am. J. Physiol. Gastrointest. Liver Physiol. · Feb 2009
TRPA1 in bradykinin-induced mechanical hypersensitivity of vagal C fibers in guinea pig esophagus.
Bradykinin (BK) activates sensory nerves and causes hyperalgesia. Transient receptor potential A1 (TRPA1) is expressed in sensory nerves and mediates cold, mechanical, and chemical nociception. TRPA1 can be activated by BK. ⋯ In contrast, esophageal vagal afferent Adelta fibers do not respond to BK or AITC and fail to show mechanical hypersensitivity after BK perfusion. This provides the first evidence directly from visceral sensory afferent nerve terminals that TRPA1 mediates BK-induced mechanical hypersensitivity. This reveals a novel mechanism of visceral peripheral sensitization.