Lack of pain associated with microfabricated microneedles.
Microscopic needles previously shown capable of transdermal delivery of drugs and proteins are demonstrated to be painless when pressed into the skin of human subjects.
Biomedical subjects
Publications and source records attributed to A H Hord.
Microscopic needles previously shown capable of transdermal delivery of drugs and proteins are demonstrated to be painless when pressed into the skin of human subjects.
Phentolamine, a nonspecific alpha 1- and alpha 2-adrenergic antagonist, relieves pain in patients with reflex sympathetic dystrophy. We sought to determine whether phentolamine, prazosin (alpha 1 antagonist), or SKF86466 (alpha 2 antagonist) relieve thermal hyperalgesia in rats with neuropathic pain. Four days after producing a chronic constriction injury (CCI), thermal hyperalgesia was tested by measuring paw withdrawal latency (PWL). After injection of phentolamine, prazosin, or SKF86466 each at doses of 1, 2, or 5 mg/kg, PWL tests were measured at 5 min and repeated at 15-min intervals for 1 h. Phentolamine, prazosin, and SKF86466 1, 2, and 5 mg/kg provided statistically significant analgesia in rats with CCI for at least 65 min. PWL did not return to baseline levels after 1 or 2 mg/kg of prazosin or SKF86466 but did so after 35 min after phentolamine 2 mg/kg. After 5 mg/kg, PWL returned to preoperative values between 5 and 50 min for phentolamine, at 35 and 65 min for prazosin, and at 50 min for SKF86466. We conclude that both alpha1 and alpha2 peripheral receptors of the sympathetic nervous system are involved in the thermal hyperalgesia caused by CCI and that thermal hyperalgesia can be reversed by both alpha1 and alpha2 antagonists in a dose-dependent manner.
IMPLICATIONS: Tizanidine was given systemically to rats with experimental postoperative pain. Partial pain relief was obtained, but the effect was not clinically significant. Although systemic tizanidine is effective in relieving experimental neuropathic pain, it is not as effective for postoperative pain.
UNLABELLED: We sought to determine whether tizanidine, an alpha2-agonist, relieved thermal hyperalgesia in rats with surgically induced neuropathic pain. We used a Sprague-Dawley rat model in which a chronic constriction of the sciatic nerve caused the rats to develop postural changes, mechanical allodynia, and thermal hyperalgesia. Thermal hyperalgesia was verified through paw withdrawal latency (PWL). PWL was tested before surgery, after surgery, and after injections with tizanidine (0.5, 1.0, or 2.0 mg/kg) or normal saline. Ambulatory and total movements were evaluated by placing the rats in activity cages. Thermal hyperalgesia was induced in all rats after surgery. Tizanidine, but not saline, caused a significant improvement in PWL (P < 0.05), with complete reversal of thermal hyperalgesia at all doses on postoperative Day 6. Rats who received tizanidine 2 mg/kg maintained complete reversal of thermal hyperalgesia through postoperative Day 9. Some sedation was observed with tizanidine 2 mg/kg, but not with smaller doses. We conclude that tizanidine effectively reversed thermal hyperalgesia in a rat model. IMPLICATIONS: This study was conducted to determine whether tizanidine could attenuate the thermal hyperalgesia that occurs in rats with surgically induced chronic constriction of the sciatic nerve. Tizanidine was effective in reducing sensitivity to heat, as measured by paw withdrawal latency, and did not cause sedation at smaller doses.
UNLABELLED: We compared the relative efficacy of the combination of the single-isomer local anesthetic levobupivacaine and the opioid analgesic morphine versus both drugs alone for postoperative epidural analgesia after major abdominal surgical procedures. Thoracic epidural anesthesia was produced and maintained with levobupivacaine 0.75% in combination with general inhaled anesthesia without opioids. Patients were randomized to one of three postoperative treatment groups: 1) a combination of levobupivacaine 0.25% and morphine 0.005%; 2) levobupivacaine 0.25%; or 3) morphine 0.005%. Postoperatively, all epidural infusions were commenced at a rate of 4 mL/h. Patients could receive a 4 mL-bolus dose and an increase in the epidural infusion rate by 2 mL/h on request for supplemental analgesia. Patients were also allowed ketorolac as a supplemental analgesic at any time after the first analgesic request. Patients in the combination group had longer times to request for supplemental analgesia as compared with the levobupivacaine only group (P < 0.05) and a trend toward longer time to request as compared with the morphine only group (P = 0.066). Patients in the combination group had lower visual analog scale pain scores at rest and activity at 4 and 8 h and fewer requests for supplemental ketorolac (P < 0.05). In conclusion, this study demonstrates a significant improvement in postoperative analgesic efficacy with the combination of levobupivacaine and morphine for continuous epidural analgesia after major abdominal surgical procedures. IMPLICATIONS: A significant improvement in postoperative analgesic efficacy is demonstrated with the thoracic epidural administration of the combination of the single-isomer local anesthetic levobupivacaine 0.25% and morphine 0.005% in patients after major abdominal surgical procedures as compared with either drug used alone.
UNLABELLED: This study was performed to determine the changes in perfusion that occur after chronic constriction injury (CCI). Male Sprague-Dawley rats weighing 275-300 g had loosely constricting ligatures placed around the left sciatic nerve. Paw withdrawal latency (PWL) to heat, skin temperature, and skin perfusion (laser Doppler) of the hind paws were measured before and for 30 days after CCI. PWL decreased significantly on the side of the CCI (maximum of 34% decrease on Postoperative Day [POD] 3), then returned to normal over a 20-day period. Skin temperature initially increased on the side of CCI, then decreased with respect to the control limb on PODs 20-30. Despite the initial increase in skin temperature on the side of CCI, skin perfusion significantly decreased immediately after CCI (maximum of 51% decrease on POD 6). The perfusion gradually returned to normal over 20 days. Because return to normal perfusion occurred while the skin temperature became colder than the control side, we conclude that there is no relationship between paw surface temperature and perfusion. IMPLICATIONS: Our data suggest that loss of sympathetic tone in thermoregulatory arteriovenous anastomoses leads to decreased nutritional blood flow to the skin of the affected limb after chronic constriction injury, which is consistent with the findings reported in humans with reflex sympathetic dystrophy.
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Patients with reflex sympathetic dystrophy, who received transient pain relief from stellate ganglion blocks or lumbar sympathetic blocks and had abnormal isolated cold stress tests, were enrolled in a study to determine the efficacy of intravenous regional bretylium. Each patient received two control treatments (0.5% lidocaine) and two treatments with 0.5% lidocaine and bretylium 1.5 mg/kg in a randomized, double-blind fashion. A standard intravenous regional technique was used with a 300-mm Hg tourniquet pressure for 20 min. Patients kept a daily record of pain relief (0 = no relief, 100% = complete relief). A decrease in pain of more than 30% was considered clinically significant. Therefore, once the patient's pain relief was less than 30%, the next intravenous regional treatment was performed. Bretylium and lidocaine provided more than 30% pain relief for a mean of 20.0 (+/- 17.5) days, whereas lidocaine alone provided relief for only 2.7 (+/- 3.7) days (Mann-Whitney U-test, P less than 0.001). A mean temperature increase in the treated limb of +2.64 +/- 3.41 degrees C above the baseline temperature was noted after bretylium administration, whereas after control treatments the change was -0.086 +/- 1.30 degrees C (Mann-Whitney U-test, P less than 0.02). We conclude that the combination of bretylium and lidocaine is significantly more effective than lidocaine alone when an intravenous block is used to treat reflex sympathetic dystrophy.
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The acute ventilatory response to spontaneously inhaled cigarette smoke (750 ml, 10% concentration) was studied in 92 experiments on 6 awake resting dogs. Upon the first or second breath of smoke inhalation, either an apnea or an augmented breath was elicited consistently in each dog, and a hyperpnea occurred subsequently. Minute ventilation (VE) increased from a base line of 3.2 to a peak of 23.9 l/min at 8.3 s (mean values) after the smoke was completely inhaled and returned toward base line in 1-3 min. Cold blocking of both vagi (exteriorized in skin loops) eliminated the initial change in breathing pattern but did not significantly reduce the delayed hyperpnea. Denervation of carotid body chemoreceptors alone abolished 71.5% of the increase in VE induced by cigarette smoke. These results suggest that the apnea or augmented breath immediately following the smoke inhalation is mediated through vagal afferents, whereas the delayed hyperpnea results primarily from the stimulation of carotid body chemoreceptors, presumably by the absorbed nicotine.
In a study designed to determine the spread of anesthetic solutions in the intercostal space, the spread of india ink was studied in fresh cadavers. They were turned prone and had epidural catheters placed at ribs 4, 6, 8 and 10, 7-8 cm lateral to the midline, by two different techniques. Group 1 had epidural catheters directed laterally into the subcostal groove. Group 2 had catheters directed medially into the intercostal space. A window was dissected in the anterior chest wall to visualize the location of the catheters and the spread of india ink. Catheters in Group 1 were observed to be lateral to the medial border of the intercostalis intimus muscle and injection of india ink resulted in spread entirely within a single intercostal space. Catheters in Group 2 were observed to be 2-3 cm medial to the border of the intercostalis intimus muscle and injection of ink resulted in concentric spread over 3-5 intercostal spaces. Posteroanterior and lateral radiographs taken with contrast material in live patients confirmed these patterns of spread. The catheters in Groups 1 and 2 were within the same tissue plane. The results indicate that the pattern of spread obtained by injection of fluid in the intercostal space is dependent upon the site of injection in relation to the angle of the rib.
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