Aysen Yucel

Effects of pulsed versus conventional radiofrequency current on rabbit dorsal root ganglion morphology

Lesioning using radiofrequency (RF) current has been increasingly used in clinical practice for the treatment of pain syndromes. Although formation of heat causing “thermocoagulation” of the nervous tissues is thought to be responsible of the clinical outcome, a more recent modality of RF application named pulsed radiofrequency (PRF) delivers the RF current without producing destructive levels of heat. In our study, we compared the effects of conventional RF (CRF) and PRF on rabbit dorsal root ganglion (DRG) morphology, including also control and sham operated groups. The setting of the experiment and the RF parameters used were similar to those used in current clinical practice. The specimens were analyzed both with light microscopy and electron microscopy, two weeks after the procedure. At the light microscopic level, all groups had preserved the normal DRG morphology and no differences were observed between them. In the electron microscopic analysis there were no pathological findings in the control and sham operated groups. But the ganglion cells in the RF groups had enlarged endoplasmic reticulum cisterns and increased number of cytoplasmic vacuoles which were more evident in the CRF group. Some of the ganglion cells in the CRF group had mitochondrial degeneration, nuclear membrane disorders or loss of nuclear membrane and neurolemma integrity. The myelinated and unmyelinated nerve fibers were of normal morphology in all groups. Our results suggest that PRF application is less destructive of cellular morphology than CRF at clinically used “doses”. Before making certain judgements, more experimental and clinical studies should be planned.

The effect of venlafaxine on ongoing and experimentally induced pain in neuropathic pain patients: a double blind, placebo controlled study

Background and aim The aim of this randomized double blind placebo controlled study was to investigate the effectiveness and the safety of venlafaxine XR 75 and 150 mg on ongoing pain and on quantitative sensory tests in 60 patients with neuropathic pain for 8 weeks.

Neurotoxicity of midazolam in the rabbit

Safe and efficient use of spinal drugs requires neurotoxicologic animal studies before ethical application. We have evaluated the neurotoxicologic interruptions of intrathecal administration of midazolam in rabbits. Eighteen white New Zealand rabbits were randomly assigned into three groups consisting of six rabbits each. In conscious animals, 0.3 ml 0.9% normal saline solution, 0.3 ml 0.1% midazolam (Roche, Dormicum) or 0.3 ml preservative free midazolam were intrathecally administered. Light and fluorescence microscopy evaluations were performed on transverse spinal cord sections by a neurohistopathologist in a blind fashion. Midazolam and preservative free midazolam treated rabbits showed significant histologic changes in light and fluorescence microscopy. The histologic and vascular lesions with the use of midazolam and preservative free midazolam suggested neurotoxic effects; thus chronic intrathecal administration of midazolam should be avoided in humans.

Transdiscal approach for hypogastric plexus block.

Background and Objectives In this study, we have performed hypogastric plexus block using a posterior transdiscal approach in 20 patients diagnosed with pelvic pain because of cancer. Methods The L5-S1 interdiscal space was identified with fluoroscopy. A needle attached to a 5-mL syringe was introduced through the disc and advanced under lateral fluoroscopic control until resistance was lost. After verifying proper position, 5 mL of 10% aqueous phenol was administered through the needle. After drawing back the needle, cephazolin 50 mg in 1 mL was administered to the disc to prevent discitis. The visual analog scale (VAS) values, daily analgesic requirements, and patient satisfaction were evaluated before the procedure, at 24 hours and then every month for 3 months after the procedure. Results Disc puncture was performed without difficulty in all patients, there were no complications associated with disc puncture such as discitis or disc rupture. Twelve patients had statistically significant pain relief immediately after the block (P < .05). Fifteen patients were satisfied after the block, and their daily analgesic requirement decreased significantly. No pain relief was observed in 5 patients. Conclusions Transdiscal approach to the hypogastric plexus appears to be a safe and effective procedure. However, prospective randomized controlled studies comparing different approaches are needed to increase our knowledge of hypogastric plexus block.

Heat hyperalgesia in humans: assessed by different stimulus temperature profiles

The aim of the present study was to investigate the effect of the rate of temperature increase on the intensity of the evoked pain before and after hyperalgesia induced by topical capsaicin. Further, hyperalgesia to suprathreshold heat stimuli was investigated. Thirteen healthy volunteers were included in the experiment. All stimuli were applied in randomised order within the volar surface of both forearms using a computer‐controlled contact stimulator. In one of the forearms, the effect of the rate of temperature change was investigated for 1.0, 5.0, and 8.0 °C/s reaching a peak temperature of 30.0, 33.0, 36.0, 39.0, and 42.0 °C in the primary hyperalgesic area and reaching a peak temperature of 33.0, 36.0, 39.0, 42.0, 45.0, 47.0, and 49.0 °C in the secondary hyperalgesic area before and after the induction of hyperalgesia. In the other forearm, the same procedure was repeated without capsaicin application as a control measurement. After the induction of hyperalgesia, the pain ratings were significantly higher in the arm treated with capsaicin compared with baseline for 36, 39, and 42 °C heating rates in the primary hyperalgesic area. The pain ratings were significantly higher with 1 °C/s heating rate compared with 5 and 8 °C/s for 36, 39, and 42 °C in the primary hyperalgesic area. Heat hyperalgesia was also observed within the secondary hyperalgesic area to pin‐prick for stimulus temperatures of 45, 47, and 49 °C compared with the baseline measurements. Increased ratings were found for all three heating rates in the secondary hyperalgesic area. There were no heat hyperalgesia in the control arm. In conclusion, hyperalgesia to suprathreshold heat stimuli was observed in the secondary hyperalgesic area and C‐fibres play an important role in the primary hyperalgesia to heat.

Secondary heat hyperalgesia detected by radiant heat stimuli in humans: evaluation of stimulus intensity and duration

Diverging observations on secondary hyperalgesia to heat stimuli have been reported in the literature. No studies have investigated the importance of heat stimulus intensity and duration for the assessment of secondary heat hyperalgesia. The present study was designed to investigate systematically (1) if pain sensitivity to radiant heat stimuli (focused Xenon light) is altered in the area of secondary punctuate hyperalgesia induced by intradermal injection of capsaicin and (2) if heat stimulus duration and intensity had an influence on the ability to detect secondary heat hyperalgesia. Pain ratings to radiant heat stimuli from a focused xenon lamp were assessed within the area of secondary punctuate hyperalgesia in fifteen volunteers before and after intradermal injection of capsaicin. The stimulus conditions were systematically varied between three intensity levels (0.8, 1.0 and 1.2 × heat pain threshold (PT)) and four duration steps (200, 350, 500 and 750 ms). The present study shows that long duration (350–750 ms) and low intensity (0.8 and 1.0 × PT) radiant heat stimuli were adequate to detect secondary heat hyperalgesia.

Comparison of hyperalgesia induced by capsaicin injection and controlled heat injury: effect on temporal summation

The relationship between induction of central sensitization and facilitation of temporal summation to repetitive stimulation is still unclear. The aim of this study was to investigate temporal summation before and after the induction of secondary hyperalgesia by two different experimental methods: capsaicin injection and controlled heat injury. The effect of each injury model was assessed on a separate day with an interval of at least 5 days. Twelve healthy volunteers participated. Each experiment was performed using electrical, radiant heat, mechanical impact, and punctuate stimuli consecutively. The pain threshold (PT) to a single stimulus and the summation threshold to five repetitive stimuli for electrical (2 Hz) and radiant heat (0.83 Hz) were assessed within the secondary hyperalgesic area. The degree of temporal summation for stimulus intensities of 0.8, 1.0, and 1.2 times the baseline pain thresholds were evaluated by the increase in visual analogue scale (VAS) scores from the first to the fifth stimulus of the train. Further, the degrees of temporal summation were assessed for mechanical impact and punctuate stimuli within the primary and secondary hyperalgesic areas. The contra-lateral forearm served as control (no injury). The pain threshold and the summation threshold to electrical and heat stimuli decreased significantly within the secondary hyperalgesic area after the injury induced by both heat injury or capsaicin injection. However, there was no temporal summation for heat and electrical stimuli in either model. In contrast, for the mechanical impact and punctuate mechanical stimuli the degree of temporal summation was significantly facilitated in the secondary hyperalgesic areas compared with the baseline and the control arm in both models. In the primary hyperalgesic area, the degree of temporal summation was facilitated to mechanical impact and punctuate stimuli but only following the capsaicin injection. In conclusion, the temporal summation mechanism for mechanical stimuli was facilitated in the secondary hyperalgesic area.

The effect of heat conditioning of the primary area before and after induction of hyperalgesia by topical/intradermal capsaicin or by controlled heat injury

The aim of the present study was to test the effect of heat conditioning before and after the induction of hyperalgesia. Three different methods were used for induction of hyperalgesia, topical capsaicin, intradermal capsaicin injection, and a controlled heat injury. The vascular (blood flow and skin temperature) and sensory changes (area of secondary hyperalgesia and ongoing pain) associated with the cutaneous hyperalgesia were compared. Each experiment consisted of two randomized sessions separated by at least 2 days. In one session, pre-conditioning of the skin by heat was performed 30 min before the induction of hyperalgesia using a probe at 45°C for 5 min in the center of the expected primary hyperalgesic area. After the induction of hyperalgesia, heat conditioning was performed twice in the center of the primary hyperalgesic area using a temperature of 2°C above the present individual pain threshold. On the contra-lateral arm, no heat conditioning was applied while hyperalgesia was induced using the same method. This session was evaluated as a control. The preconditioning induced an increased skin temperature in the primary area for both topical capsaicin and the controlled heat injury. Postconditioning caused increased blood flow in the secondary hyperalgesic area for the topical capsaicin method and increased blood flow in the primary hyperalgesic area for the controlled heat injury method. However, conditioning with heat in an attempt to increase the C-fiber input did not have any effect on the ongoing pain ratings and sensory test results in any of the methods. The results of the present study suggest that there is still a need for a better experimental model with more stable allodynia both between sessions and between subjects while at the same time minimizing discomfort to the volunteer.The aim of the present study was to test the effect of heat conditioning before and after the induction of hyperalgesia. Three different methods were used for induction of hyperalgesia, topical capsaicin, intradermal capsaicin injection, and a controlled heat injury. The vascular (blood flow and skin temperature) and sensory changes (area of secondary hyperalgesia and ongoing pain) associated with the cutaneous hyperalgesia were compared. Each experiment consisted of two randomized sessions separated by at least 2 days. In one session, pre-conditioning of the skin by heat was performed 30 min before the induction of hyperalgesia using a probe at 45 degrees C for 5 min in the center of the expected primary hyperalgesic area. After the induction of hyperalgesia, heat conditioning was performed twice in the center of the primary hyperalgesic area using a temperature of 2 degrees C above the present individual pain threshold. On the contra-lateral arm, no heat conditioning was applied while hyperalgesia was induced using the same method. This session was evaluated as a control. The pre-conditioning induced an increased skin temperature in the primary area for both topical capsaicin and the controlled heat injury. Post-conditioning caused increased blood flow in the secondary hyperalgesic area for the topical capsaicin method and increased blood flow in the primary hyperalgesic area for the controlled heat injury method. However, conditioning with heat in an attempt to increase the C-fiber input did not have any effect on the ongoing pain ratings and sensory test results in any of the methods. The results of the present study suggest that there is still a need for a better experimental model with more stable allodynia both between sessions and between subjects while at the same time minimizing discomfort to the volunteer.