Effects of age and size on development of allodynia in a chronic pain model produced by sciatic nerve ligation in rats.

Sciatic nerve constriction injury in rats has been used by various investigators as a model of chronic pain exhibiting allodynia and hyperalgesia. Although rats ranging between 200 and 350 g (40-70 days old) at the time of operation have been used by various investigators, the effect of rat age and weight on the model has not been previously studied. We noted that a group of older rats failed to develop all the characteristics of the model and designed the present study to determine the effect of age and weight on the development of allodynia and hyperalgesia. Three groups of rats varying in age (54, 71, and 107 days) and weight (220-250 g, 270-350 g, and 370-470 g) with the experimental lesion were tested for hyperalgesia, cold allodynia, and tactile allodynia. We found that although the degree of hyperalgesia of all groups was the same, the oldest group had significantly longer response latencies to allodynia tests than the younger 2 groups. Responses to the cold test were no different than control in the oldest group. The results of the present study demonstrate that larger, older rats fail to develop allodynia after sciatic nerve ligation.

Effect of intrathecal tizanidine on antinociception and blood pressure in the rat.

Experiments were performed in rats to determine if the alpha 2-adrenergic agonist tizanidine has an antinociceptive effect when injected intrathecally, and whether the analgesia is accompanied by changes in blood pressure. Rats were chronically implanted with catheters in the lumbar subarachnoid space. Antinociception was evaluated in conscious rats with the tail-flick test. Increasing tizanidine doses produced increases in analgesic efficacy, with 25 micrograms producing a significant long-lasting antinociception. This tail-flick analgesia was very similar to that produced by clonidine (25 micrograms) and morphine (8 micrograms) in peak effect and duration. Doses as high as 250 micrograms produced only a transient hind limb motor dysfunction in 43% of the animals. Daily injections of 25 micrograms tizanidine over 5 days produced a decrease in antinociception, with the peak effect at day 5 at 59% of that at day 1. Blood pressure, in rats lightly anesthetized with halothane, was not affected by tizanidine injections up to 250 micrograms. Tizanidine appears to be a promising non-opiate analgesic for intrathecal usage.

A comparison of cryoprobe and crush lesions in the rat sciatic nerve.

This study examines the behavioral, sensory, motor and structural recovery during the first 2 months following a freeze (cryoprobe) lesion compared to a nerve crush (forceps). There is a complete loss of sensory and motor function following either type of lesion during the first 2 weeks of recovery. The toe spreading reflex and the sciatic functional index of locomotion behavior returned to normal without significant group differences. Latency times for the pain withdrawal reflex were slightly shorter in the cryoprobe group, but both groups returned to baseline during the second month. An improved regenerative pattern was suggested for the motor recovery in the cryoprobe group as expressed by the amplitude of the digital twitch tension curves. However, the respective curve areas were not different. Morphometric analysis indicated a significant reduction in the distal nerve cross-sectional area, an increase in the mean myelinated fiber density and an increase in the estimated total number of myelinated nerve fibers in both experimental groups. Mean fiber diameter and myelin sheath thickness had not fully returned to normal in either experimental group. Both the fiber size and myelin sheath thickness were significantly reduced in the cryoprobe group. In conclusion, the two lesion types have remarkably similar patterns of recovery. Functional data suggest that motor recovery precedes sensory recovery following a cryoprobe lesion.

Psychological differences between reflex sympathetic dystrophy and non-RSD chronic pain patients.

This study examined possible psychological differences between Reflex Sympathetic Dystrophy (RSD) and non-RSD chronic pain patients. Unlike the few previous studies in this area, this study controlled statistically for age and pain duration differences across diagnostic groups, and included a non-RSD limb pain control group. Subjects were a consecutive series of 34 RSD, 50 non-RSD limb pain (Limb), and 165 low back pain (LBP) patients presenting for treatment at the Rush Pain Center. Analyses revealed that RSD patients reported more somatization and phobic anxiety on the Brief Symptom Inventory than LBP patients. RSD patients also reported greater coping with pain through diverting attention than LBP patients did on the Coping Strategies Questionnaire. Comparisons between the RSD and Limb groups revealed no significant differences with the exception of somatization scores. The relationship between distress and pain severity was found to be stronger in RSD and Limb patients than in LBP patients. These results provide partial support for clinical assumptions that RSD patients are more psychologically dysfunctional than other chronic pain patients. However, these conclusions do not generalize across all comparison groups. The fact that RSD and non-RSD limb pain patients were quite similar on nearly all measures suggests that sympathetic mediation of pain is not the source of these psychological differences.

The antinociceptive and histologic effect of sciatic nerve blocks with 5% butamben suspension in rats.

UNLABELLED: Butamben, a lipophilic local anesthetic of the ester class, produces a differential nerve block of long duration. Epidural and peripheral nerve blocks with butamben, formulated as a 5%--10% suspension, result in prolonged analgesia without significant motor blockade. We evaluated the effect of butamben sciatic nerve block on antinociception using the rat paw formalin test, as well as withdrawal latencies to thermal stimulation, and assessed histologic changes in the nerve. After right sciatic nerve block with butamben 5% or saline, responses to intradermal injection of 5% formalin were recorded in randomly selected groups of 6 animals each on days 1, 2, 5, 10, 21, and 28. In an additional group of 8 thermal challenges to both hind paws were recorded at 1, 2, 5, 7, 10, 14, 17, 21, and 28 days after right sciatic butamben 5% blocks. Butamben injection decreased the formalin-induced flinches on days 2, 5, 10, 21 and 28 and decreased thermal challenges on days 1 through 17. Histologic changes were minimal. This study demonstrates a prolonged antinociceptive effect from butamben nerve block to both formalin-induced nociception and heat hyperalgesia, without an effect on gross motor function or histologic morphology. IMPLICATIONS: Butamben 5% nerve blocks produced a prolonged antinociceptive effect to formalin-induced nociception and heat hyperalgesia, without significant motor effect or evidence of substantial histologic changes.

The mechanisms of intracranial pressure modulation by epidural blood and other injectates in a postdural puncture rat model.

UNLABELLED: The epidural blood patch is considered effective in treating postdural puncture headache. We have developed a postdural puncture model in rats for quantitative evaluation of the magnitude and duration of changes in cerebrospinal fluid (CSF) pressure in the cisterna magna in response to the administration of epidural blood or other moieties. This model was used to compare the efficacy of various methods of epidural injection for restoring and maintaining CSF pressure for up to 240 min. After lumbar dural puncture, CSF pressure declined 3.6 +/- 0.2 mm Hg. Epidural saline (100 microL) injected at the puncture site initially increased pressure by 7.2 +/- 0.7 mm Hg, but it rapidly (7.8 +/- 0.6 min) returned to postdural puncture baseline. A similar initial increase of CSF pressure was observed with equal volumes of all other epidural injectates, but the duration of pressure increase varied greatly. Hetastarch and dextran 40 produced results similar to saline. Only whole blood or fibrin glue consistently increased CSF pressure for the entire 240-min observation period. Whole blood mixed with anticoagulant or injected 20-mm cephalad to the puncture site did not sustain pressure. After laminectomy, direct application of blood or adhesive to the dural defect caused no pressure increase. Continuous infusion of saline after bolus could maintain pressure increase for 180 min, but within 60 min of stopping infusion, pressure returned to baseline. These results confirm the efficacy of the epidural administration of blood or fibrin glue to correct CSF hypotension after dural puncture and also provide insight into the mechanisms of intracranial pressure modulation. Sealing the dural defect does not effectively correct CSF pressure unless an epidural tamponade effect is also maintained. IMPLICATIONS: A rat model was developed to evaluate different drugs that may be injected epidurally to treat postdural puncture headache. Epidural injection of blood or fibrin glue was the most effective method of maintaining increased cerebrospinal fluid pressure after dural puncture. Sealing the dural defect does not effectively correct cerebrospinal fluid pressure unless an epidural tamponade effect is maintained.

Continuous intrathecal clonidine and tizanidine in conscious dogs: analgesic and hemodynamic effects.

UNLABELLED: Alpha-2-adrenergic agonists, such as clonidine, produce antinociception in animal pain models after intrathecal administration. However, clinical usage is limited by cardiovascular side effects. To investigate alternative alpha(2)-adrenergic agonists as analgesics, we implanted six dogs with an intrathecal catheter and infusion pump. After baseline saline infusion, animals received clonidine or tizanidine (crossover study) each week at escalating doses of 125-750 microg/h. Analgesia, blood pressure, heart rate, respiratory rate, sedation, and coordination were evaluated. A 28-day safety study was performed with another nine dogs receiving intrathecal tizanidine (3 or 6 mg/d) or saline. Equal doses of clonidine and tizanidine produce the same antinociception in thermal withdrawal tests. Blood pressure was reduced with 125-500 microg/h of clonidine, but not with tizanidine at any dose. Clonidine 250 microg/h reduced heart rate by 45.8%, and five of six animals had bradyarrhythmias (marked bradycardia), whereas tizanidine decreased heart rate by 15.1% without arrhythmias, even at the largest dose. Respiratory rate decreased with 250 microg/h of clonidine and larger doses. Sedation or incoordination occurred only at the largest dose for either drug. The safety study indicated that 3 mg/d of tizanidine in dogs produced no side effects or histopathologic changes. Tizanidine may be a useful alternative in patients experiencing cardiovascular side effects with intrathecal infusion of clonidine. IMPLICATIONS: Clonidine is an effective spinal analgesic, but it is dose-limited by cardiovascular side effects. We compared the analgesic properties and side effects of clonidine with those of a similar drug, tizanidine. Continuous spinal infusion of tizanidine produced similar analgesia as clonidine, but with fewer adverse effects on blood pressure and heart rate.