Absence of Histological Changes after the Administration of a Continuous Intrathecal Clonidine in Wistar rats

Background:   The administration of epidural and spinal clonidine has demonstrated an antinociceptive effect in animals and humans. For that reason, its spinal administration has been proposed as an adjuvant in chronic pain management. However, there is limited information about its possible neurotoxic effect after its continuous neuraxial administration.
Method:   Twelve male Wistar rats were randomly divided into two groups. Using an osmotic mini-pump a continuous infusion of intrathecal clonidine, (21.4 micrograms/day, Group A) or saline solution (Group B), was administered for 14 consecutive days. For evaluating the neurological damage a neuropathological analysis of the spinal cord was performed by light microscopy.
Results:   Neurohistopathologic examination of the spinal cord specimens failed to show evidence of neurotoxic damage in either group.
Conclusions:   These findings showed that continuous intrathecal administration of clonidine did not produce evidence of histological neurotoxicity; therefore it is possible that continuous administration of intrathecal clonidine might be a safe option for treatment of chronic intractable pain; however, further investigations are necessary for evaluating diverse doses and periods of time, and to define its possible behavioral effects.     

Propentofylline after focal cortical lesion in the rat: impact on functional recovery and basic fibroblast growth factor expression

The effects of propentofylline, a xanthine derivative and adenosine transport inhibitor, were evaluated following anteromedial cortex lesion in the rat. Propentofylline (2x/10 mg/kg, intraperitoneally) was administered for 7 days post-insult and basic fibroblast growth factor (bFGF) immunoreactivity measured at designated time points in the peri-lesional cortex and ipsilateral dorsal striatum. The spatiotemporal pattern of bFGF expression was then compared to functional recovery patterns. Propentofylline-treated animals displayed increased bFGF expression in the peri-lesional cortex which may have contributed to the observed early facilitation of functional recovery. Drug administration did not, however, produce a change in bFGF expression in the ipsilateral dorsal striatum compared to saline-treated animals. These findings taken together with other positive findings regarding propentofylline, support the drug's therapeutic potential.     

Practice guidelines for the management of low back pain. Consensus Group of Practice Parameters to Manage Low Back Pain

It has been documented that pain in its diverse modalities is the most common cause of medical attention. In Mexico, an increase in its frequency has promoted its consideration in several health programs. On the other hand, inadequate pain management will cause severe physical, psychoaffective, and socioeconomic repercussions for patients, families, and public health services. Despite this panorama, there has not been an agreement to establish better diagnostic and therapeutic methods for the management of chronic pain. A consensus group was reunited and was integrated by medical experts from private and public institutions and from various states of the Mexican Republic. To assure the development of these practice guidelines, these experts had experience in the assessment and treatment of conditions causing pain. With the guidelines used by other consensus groups, meetings were held to analyze and discuss published literary evidence for the management of low back pain. The recommendations were classified according to their methodological strength. As a result of this meeting, consensus recommendations were based on evidence and operational conclusions of such proactive educational plans, institutional policies and diagnostic recommendations for pharmacological and nonpharmacological treatment in order for Mexican physicians to provide a better therapeutic approach to low back pain.     

Co-administration of rofecoxib and tramadol results in additive or sub-additive interaction during arthritic nociception in rat

Over the decades, nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids are the most commonly used analgesics in the management of acute and chronic pain. In order to assess a possible antinociceptive interactions, the antinociceptive effects of rofecoxib p.o., a preferential inhibitor of cyclooxygenase-2, and tramadol-hydrochloride p.o., an atypical opioid analgesic, administered either separately or in combination, were determined using a rat model of arthritic pain. The data were interpreted using the surface of synergistic interaction (SSI) analysis and an isobolographic analysis to establish the nature of the interaction. The SSI was calculated from the total antinociceptive effect produced by the combination after subtraction of the antinociceptive effect produced by each individual drug. Female rats received orally rofecoxib alone (1.0, 1.8, 3.2, 5.6, 10.0, 17.8, 31.6 and 56.2 mg/kg), tramadol alone (1.8, 3.2, 5.6, 10.0, 17.8, 31.6 and 56.2 mg/kg) or 12 different combinations of rofecoxib plus tramadol. Five combinations exhibited various degrees of sub-additive (i.e. less than the sum of the effects produced by the each drug alone) antinociceptive effects (3.2 mg/kg tramadol with 7.8 mg/kg rofecoxib; 5.6 mg/kg tramadol with either 10.0 or 17.8 mg/kg rofecoxib; 10.0 mg/kg tramadol with either 10.0 or 17.8 mg/kg rofecoxib), whereas the other 7 combinations showed additive antinociceptive effects (i.e. the sum of the effects produced by each agent alone). Three combination of rofecoxib+tramadol (10.0+5.6, 10.0+10.0, and 17.8+5.6 mg/kg respectively) presented high sub-additive interactions (P<0.002: Q=9.5). The combination rofecoxib (17.8 mg/kg)+tramadol (10.0 mg/kg) caused gastric injuries less severe than those observed with indomethacin, but more severe than those obtained with rofecoxib or tramadol in single administration. The antinociceptive interaction of rofecoxib and tramadol suggests that combinations with these drugs may have no clinical utility in pain therapy.