The Roles of Spinal Cord Glia in Bee Venom-induced Nociception and Inflammation in Concious Rats
|School||Dalian Medical University|
|Keywords||bee venom spinal cord glia inflammation pain|
Background:The traditional opinion thought that the generation of pain only was related to neurons and neurotranmitters released from neurons. However, in the early 20th century, the important role of glia including microglia and astrocytes near the spinal cord neurons began to be paid more attentions by a lot of people, and it is proposed that the spinal cord glial cells may play a role in the develepment and maintenance of pathological pain. This new understanding began to challenge troditional“center on neuron”theory. In the past decade, a growing evidence supported the opinion that the spinal cord glia plays an important role in the inflammation and pain caused by tissue and nerve damage. Peripheral tissue injures produces pain-related behaviors (persistent spontaneous nociception and hyperalgesia ) and inflammatory reaction such as redness, edema. Our previous studies have showed that intraplantar (ipl.) injection of bee venom (BV) produced persistent spontaneous nociception (PSN) and heat and mechanical hyperalgesia, as well as obvious inflammatory swelling of the injected paw such as the redness and edema of the injected paw. Further study about the role of spinal cord gila in the pain and inflammation induced by tissue and nerve injuries will pave way for the new theraputic strategy.Objective: The present study aims to determine the roles of spinal cord glia in BV-induced nociception and inflammation, by observing the effect of pre-treatment with intrathecal glia function disruptors such as fluorocitrate and minocycline,on BV-induced persistent spontaneous nociception, mechanical hyperalgesia, and inflammatory swelling.Methods: We used BV-induced pain rat model to investigate the role of spinal cord glia in the PSN, mechanical hyperalgesia and inflammatory reaction of the injected hind paw. The experiments were performed on Sprague-Dawley male rats weighing from 200-300g. Fluorocitrate, a non-specific glia metabolism disruptor and minocycline, a specific microglia function disruptor were used in the present study. Pretreatment with intrathecal minocycline and fluorocitrate of different doses were made 20 min prior to BV injection. As control, vehicle (10μl/rat) was administrated 20min prior to BV injection. The spontaneous nocicepive behavioral response of rats was determined by counting the number of paw flinches during each 5 min interval of 1 h time course following injection of BV. Paw withdrawal mechanical threshold (PWMT) of injected hind paws by electronic von Frey was examined at time prior to drugs administration and 2h after BV injection. Change in paw volume was used as a determinant of the BV-induced inflammatory responses. Based on the principle of Archim- edes, the paw volume was measured by water displacement using a plethy- smometer (PU). Measurements were taken at time prior to drugs administration and 2h after the BV injection.Results:(1)The effect of minocycline and fluorocitrate upon BV-induced spontaneous pain. Compared with control group, pre-treatment with intrathecal injection of minocycline, a specific microglia function disruptor and fluorocitrate, a glia function disruptor, produced a significant inhibition of BV-induced spontaneous flinching reflex over the observed 1 hour, and the inhibitory effect in fluorocitrate group is dose-related over the observed 1 hour.(2)The effect of minocycline and fluorocitrate upon BV-induced mechanical hyperalgesia. Compared with vehicle group, pretreatment with intrathecal minocycline, a specific microglia function disruptor had effect on BV-induced decrease in PWMT . However, pretreatment with intrathecal fluorocitrate, a non-specific glia function disruptor produced a significant inhibitory effect on BV-induced decrease in PWMT in a dose-related manner.(3)The effect of minocycline and fluorocitrate upon BV-indced inflammation. Compared with control group, pre-treatment with intrathecal minocycline and fluorocitrate had no effect on BV-induced increase in paw volume.Conclusions:(1)spinal cord glia, espicially microglia may contribute to BV -induced PSN.(2)spinal cord microglia and/or astrocyte may be involved in BV-induced mechanical hyperalgesia.(3)spinal cord glia could not play a key role in the development of BV-induced inflammation.