Characteristics of tachyphylaxis to inhaled histamine in anesthetized dogs

Three consecutive dose-response curves to aerosolized histamine were obtained in 11 anesthetized dogs. All dogs showed desensitization (i.e., tachyphylaxis) to high doses of histamine. Tachyphylaxis was highly reproducible. No tachyphylaxis occurred with inhaled acetylcholine or methacholine. Beta-Adrenergic blockade with propranolol or muscarinic blockade with atropine given intravenously had no effect on the histamine tachyphylaxis. Duration of thiamylal anesthesia did not alter the histamine responsiveness. Histamine tachyphylaxis was also seen with chloralose-urethan anesthesia. Since tachyphylaxis is not observed with acetylcholine, it cannot be attributed to a general decline in muscle contractility. We conclude that histamine tachyphylaxis in vivo is not explained by effects of cholinergic reflexes, catecholamine release, duration of anesthesia, or, probably, type of anesthetic agent.     

Evaluation of tissue changes following intramuscular infiltration of lidocaine in rainbow trout Oncorhynchus mykiss

Rainbow trout Oncorhynchus mykiss were infiltrated with either saline or lidocaine adjacent to the dorsal fin to assess histopathological changes. Infiltration was done as if it were being used as a local anaesthetic. Tissue lesions and associated tissue healing were examined over a period of 30 days. Most changes occurred at the cranial site of where the solution was first infiltrated. The infiltration of a dose of 10 mg kg^?1 of lidocaine appears to have damaged the skeletal muscle and connective tissues more than a similar volume of saline, especially during the first 15 days. The primary changes included haemorrhage, inflammation and muscle degeneration and necrosis. By day 30 post‐infiltration inflammatory lesions were either nearly or completely absent, signs of myofibre regeneration were noted in only one fish. This experiment shows local anaesthetics and saline can produce localized tissue damage, especially during the first 2 weeks post infiltration. Care should be taken to allow the fish to heal for at least 30 days and probably more, no matter the solution administered, especially if giving repeated injections or infiltrations at the same site.     

Acute physiological responses to castration-related pain in piglets: the effect of two local anesthetics with or without meloxicam

Methods to reduce castration-related pain in piglets are still issues of concern and interest for authorities and producers. Our objectives were to estimate the effectiveness of two protocols of local anesthesia (lidocaine and the combination of lidocaine+bupivacaine) as well as the use of meloxicam as a postoperative analgesic in alleviating castration-related pain, measured by acute physiological responses. Eight groups (15 piglets/group) were included in the study: (1) castration without anesthesia or analgesia, without meloxicam (TRAD WITHOUT), (2) castration without anesthesia or analgesia, but with meloxicam (TRAD WITH), (3) handling without meloxicam (SHAM WITHOUT), (4) handling with meloxicam (SHAM WITH), (5) castration after local anesthesia with lidocaine but without meloxicam (LIDO WITHOUT), (6) castration after local anesthesia with lidocaine and meloxicam (LIDO WITH), (7) castration after local anesthesia with lidocaine+bupivacaine without meloxicam (LIDO+BUPI WITHOUT), (8) castration after local anesthesia with lidocaine+bupivacaine and meloxicam (LIDO+BUPI WITH). Acute physiological responses measured included skin surface temperature and serum glucose and cortisol concentrations. On days 4 and 11 post-castration BW was recorded and average daily gain was calculated over this period. Furthermore, piglet mortality was recorded over the 11-day post-castration period. Administration of local anesthetic or meloxicam did not prevent the decrease in skin surface temperature associated with castration. Lidocaine reduced the increase in glucose concentration associated with castration. For castrated pigs, the joint use of lidocaine and meloxicam caused a significant decrease in cortisol concentration; the combination of intratesticular lidocaine and bupivacaine did not seem to be more effective than lidocaine alone. No effect of treatments on mortality and growth were detected.     

腰丛-坐骨神经阻滞与腰硬联合麻醉用于老年患者下肢手术中的效果比较

目的:分析和比较两种不同麻醉方式(腰丛-坐骨神经阻滞麻醉与腰硬联合麻醉)对老年患者下肢骨折手术中的效果。方法:以我院收治的下肢骨折拟行手术治疗的老年患者158例作为研究对象,将其随机分为腰硬联合麻醉组(CSEA)和腰丛-坐骨神经阻滞组(LPSB),每组各79例。CSEA组采用腰硬联合麻醉,LPSB组采用腰丛-坐骨神经阻滞,比较两组患者感觉阻滞起效时间、运动阻滞起效时间、运动恢复时间、维持时间、疼痛感觉评分和并发症的发生状况。结果:CSEA组和LPSB分别有1例和3例患者因局部麻醉失效而需全身麻醉;LPSB组的感觉阻滞起效时间、运动阻滞起效时间、运动恢复时间均显著晚于CSEA组,但其维持时间显著长于CSEA组,患者疼痛感觉评分低于CSEA组(P0.05)。结论:与腰硬联合麻醉相比,腰丛-坐骨神经阻滞能为老年下肢骨折手术患者提供有效的单侧麻醉,且安全性高,可作为下肢骨科手术患者的首选麻醉方案。     

Peroxynitrite does not impair pulmonary and systemic vascular responses.

The effects of peroxynitrite (ONOO-) on vascular responses were investigated in the systemic and hindquarters vascular bed and in the isolated perfused rat lung. Intravenous injections of ONOO- decreased systemic arterial pressure, and injections of ONOO- into the hindquarters decreased perfusion pressure in a dose-related manner. Injections of ONOO- into the lung perfusion circuit increased pulmonary arterial perfusion pressure. Responses to ONOO- were rapid in onset, short in duration, and repeatable without exhibiting tachyphylaxis. Repeated injections of ONOO- did not alter systemic, hindquarters, or pulmonary responses to endothelium-dependent vasodilators or other vasoactive agonists and did not alter the hypoxic pulmonary vasoconstrictor response. Injections of sodium nitrate or nitrite or decomposed ONOO- had little effect on vascular pressures. Pulmonary and hindquarters responses to ONOO- were not altered by a cyclooxygenase inhibitor in a dose that attenuated responses to arachidonic acid. These results demonstrate that ONOO- has significant pulmonary vasoconstrictor, systemic vasodepressor, and vasodilator activity; that short-term repeated exposure does impair vascular responsiveness; and that responses to ONOO- are not dependent on cyclooxygenase product release.     

Psychophysical studies of the itch sensation and itchy skin ("alloknesis") produced by intracutaneous injection of histamine.

Psychophysical measurements of itch and itchy skin ("alloknesis"--itch produced by innocuous mechanical stimulation) were obtained in human volunteers following intracutaneous or subcutaneous injections of histamine or papain into the volar forearm. Histamine and papain were given in doses of 0.1, 1, or 10 micrograms in 10 microliters of saline. The effects of the depth of injection and of skin temperature on the latency, magnitude, and duration of itch were examined. Also, dose-response functions were obtained for the area of alloknesis produced by intracutaneous injections of histamine. Finally, the neural mechanisms underlying the spread of alloknesis were investigated via local anesthesia of the skin. Intracutaneous and subcutaneous injections of histamine, but not papain, produced a sensation of itch without pain. The latency of itch was shorter after an intracutanous than after a subcutaneous injection of histamine. The mean latencies of itch produced by a 1-microgram dose were 9.5 and 23.0 sec for intracutaneous and subcutaneous injections, respectively. No differences were observed in the magnitude or duration of itch. Similarly, the latency of itch was increased when the skin temperature at injection site was lowered to 15 degrees C, whereas the magnitude and duration of itch were unaffected. Intracutaneous and subcutaneous injections of histamine produced similar areas of alloknesis. However, the magnitude and duration of alloknesis were dependent on dose. The mean maximum areas of alloknesis produced by intracutaneous injections of 0.1, 1, and 10 micrograms of histamine were 28.3, 47.2, and 43.8 cm2, respectively. Alloknesis was present at 2 min after injection, increased to a maximum area without 10 min, and then gradually decreased during the next 25-40 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

急性神经损伤引起脊髓背角C-纤维诱发电位长时程增强

神经损伤引起神经病性疼痛,表现为持续性痛超敏和痛觉过敏。目前对神经病性疼痛的机制尚缺乏了解。我们以往的工作表明强直电刺激坐骨神经可引起脊髓背角C-纤维诱发电位的长时程增强(long-term potentiation,LTP),该LTP被认为是病理性疼痛的突触模型。本研究的目的在于探讨急性神经损伤是否能在完整动物的脊髓背角诱发出C-纤维诱发电位LTP。在以测试刺激(10～20V,0．5ms)电刺激坐骨神经的同时在脊髓背角用微电极记录C一纤维诱发电位。分别用强直刺激、剪断或夹捏坐骨神经诱导LTP。结果发现：(1)剪断或夹捏坐骨神经都可以诱导脊髓背角C-纤维诱发电位的LTP,该LTP可持续到实验结束(3～9h),在剪断神经前10min用利多卡因局部阻滞坐骨神经则可完全阻断LTP的产生;(2)神经损伤诱导的LTP可被NMDA受体阻断剂AP5所阻断;(3)用单次强直刺激引起LTP后,切断坐骨神经可使LTP的幅度进一步增大,而用多次强直电刺激使LTP饱和后,损伤神经则不能使LTP进一步增大。切断神经引起LTP后,强直电刺激也不能使LTP进一步增大。这些结果表明,急性神经损伤可以诱导脊髓背角C纤维诱发电位LTP,且切断神经能更有效地诱导LTP。该试验进一步支持我们的设想,即脊髓背角C-纤维诱发电位LTP可能在病理性疼痛的形成中起重要作用。     

Effects of cold dry air nasal stimulation on airway mucosal blood flow in humans

Several studies have demonstrated that nasal challenges can induce reflex responses in the respiratory system. Some authors have described bronchoconstriction and modification of the pattern of breathing following nasal challenges by irritants and cold air. We propose to determine the effect of nasal stimulation with cold dry air on airway mucosal blood flow (Qaw) in the proximal tracheal bronchial tree of healthy humans. Nine healthy subjects participated in the study. Baseline measurement Qaw, nasal airway resistance (NAR) and airway caliber by specific airways conductance (SGaw) were followed by nasal challenge with cold dry air. Qaw, NAR and Sgaw were determined after the challenge. In those subjects in which a significant decline in Qaw was recorded the protocol was repeated after pretreatment with nasal anesthesia using topical lidocaine. Cold dry air challenge produced a significant decrease in mean Qaw for the nine subjects and this response was abolished by pretreatment with nasal anesthesia using topical lidocaine. There was no significant change in Sgaw and NAR after the challenge and topical lidocaine anesthesia. Our data indicates that nasal stimulation with cold dry air leads to a reduction in Qaw and that this effect may be mediated by a nasal reflex.     

Do not use epinephrine in digital blocks: myth or truth?

The purpose of this study was to examine the role for epinephrine augmentation of digital block anesthesia by safely prolonging its duration of action and providing a temporary hemostatic effect. After obtaining approval from the review board of the authors' institution, 60 digital block procedures were performed in a prospective randomized double-blinded study. The digital blocks were performed using the dorsal approach. All anesthetics were delivered to treat either posttraumatic injuries or elective conditions. Of the 60 digital block procedures, 31 were randomized to lidocaine with epinephrine and 29 to plain lidocaine. Of the procedures performed using lidocaine with epinephrine, one patient required an additional injection versus five of the patients who were given plain lidocaine (p = 0.098). The need for control of bleeding required digital tourniquet use in 20 of 29 block procedures with plain lidocaine and in 9 of 31 procedures using lidocaine with epinephrine (p < 0.002). Two patients experienced complications after plain lidocaine blocks, while no complications occurred after lidocaine with epinephrine blocks (p = 0.23). By prolonging lidocaine's duration of action, epinephrine may prevent the need for an additional injection and prolong post-procedure pain relief. This study demonstrated that the temporary hemostatic effect of epinephrine decreased the need for, and thus the potential risk of, using a digital tourniquet (p < 0.002). As the temporary vasoconstrictor effect is reversible, the threat of complication from vasoconstrictor-induced ischemia is theoretical.     

Age-related variations of elements as compared among optic, radial, and sciatic nerves

To elucidate changes of peripheral nerves with aging, the authors studied age-related changes of element contents in the optic, radial, and sciatic nerves by inductively coupled plasma-atomic emission spectrometry. The subjects consisted of seven men and seven women, ranging in age from 61 to 97 yr. The contents of phosphorus and sulfur remained constant through ages 61 to 97 yr in three nerves, the optic, radial, and sciatic nerves. It was found that there were age-related differences in calcium content among the optic, radial, and sciatic nerves: The calcium content of the optic nerve increased progressively with aging; in the radial nerve, it was hardly changed with aging; in contrast, the calcium content of the sciatic nerve decreased gradually with aging. In addition, it was found that in the radial nerve there were moderate correlations between age and zinc or sodium content, whereas significant correlations between age and the content of silicon or iron were found in the sciatic nerve. Furthermore, there was a correlation between the silicon and iron contents in the sciatic nerves.     

Nasal and tracheal responses to chemical and somatic afferent stimulation in anesthetized cats

Respiratory chemical and reflex interventions have been shown to affect nasal resistance or tracheal tone, respectively. In the present study, nasal caliber (assessed from pressure at a constant flow) and tracheal tone (assessed from pressure in a fluid-filled balloon within an isolated tracheal segment) were monitored simultaneously in anesthetized, paralyzed, artificially ventilated (inspired O2 fraction = 100%) cats. We examined the effect of CO2 inhalation and sciatic nerve stimulation as well as the application of nicotine (6 X 10(-4) mol/l) or lidocaine (2% solution) to the intermediate area of the ventral medullary surface (VMS). CO2 and VMS nicotine resulted in a significant increase in tracheal pressure [147 +/- 73 and 91 +/- 86% (SD), respectively]; and a significant reduction in nasal pressure (-35 +/- 10 and -20 +/- 13%, respectively). In contrast, sciatic nerve stimulation resulted in a significant fall in both tracheal (-50 +/- 36%) and nasal pressure (-21 +/- 13%). Application of 2 or 4% lidocaine to the VMS reduced tracheal pressure but did not significantly affect nasal pressure. After VMS lidocaine, nasal and tracheal responses to CO2, sciatic nerve stimulation, or VMS nicotine, when present, were negligible. These results suggest a role for the VMS in the regulation and coordination of nasal and tracheal caliber responses.     

Histamine tachyphylaxis in canine airways despite prostaglandin synthesis inhibition

Tachyphylaxis to aerosolized histamine was studied in dogs anesthetized with thiamylal after pretreatment with prostaglandin synthesis inhibitors. Three consecutive histamine dose-response curves were obtained in nine dogs pretreated with 5 mg/kg indomethacin; two of these nine were also pretreated with 10 mg/kg indomethacin. Seven of the nine dogs were pretreated with 4 mg/kg sodium meclofenamate; four of these seven were also pretreated with 12 mg/kg. All dogs had tachyphylaxis at high concentrations of histamine regardless of inhibitor used. Pretreatment with indomethacin while the dogs were under alpha-chloralose-urethan anesthesia gave similar results. Histamine tachyphylaxis was also studied both in the presence and in the absence of indomethacin in tracheal smooth muscle strips obtained from seven additional dogs. A decrease in the median effective dose to histamine was observed in the indomethacin-treated strips, but tachyphylaxis to histamine remained. We conclude that prostaglandin synthesis inhibition does not reverse histamine tachyphylaxis either in vivo or in vitro. Thus the mechanism of histamine tachyphylaxis remains unexplained.     

对比分析超声引导下椎旁神经阻滞与肋间神经阻滞在脊柱手术患者应用效果及对血流动力学的影响

摘要 目的：对比分析超声引导下椎旁神经阻滞与肋间神经阻滞在脊柱手术患者应用效果及对血流动力学的影响。方法：选择西安交通大学第一附属医院2020年6月至2021年12月收治的脊柱骨折患者96例作为研究对象,根据1:1随机数字表法把患者分为椎旁神经阻滞组与肋间神经阻滞组各48例。所有患者均给予脊柱手术治疗,所有手术操作都由同一组医生完成,椎旁神经阻滞组与肋间神经阻滞组分别给予超声引导下椎旁神经阻滞与肋间神经阻滞,记录两组阻滞效果及对血流动力学的影响。结果：两组通气5 min、通气30 min、恢复双肺通气30 min等时间点的HR、SPO₂值在组内与组间对比无差异（P>0.05）。两组的术中补液量、术中出血量、手术时间、麻醉时间、术中尿量等对比无差异（P>0.05）。椎旁神经阻滞组的坐骨神经运动神经、感觉神经阻滞持续时间都少于肋间神经阻滞组（P<0.05）,两组运动神经、感觉神经阻滞起效时间对比无差异（P>0.05）。椎旁神经阻滞组术后7 d的肺部感染、肺栓塞、呼吸衰竭等肺部并发症发生率2.1 %,低于肋间神经阻滞组的16.7 %（P<0.05）。结论：相对于肋间神经阻滞,超声引导下椎旁神经阻滞在脊柱手术患者并不会影响患者的血流动力学状况,也不会影响手术与麻醉过程,还可缩短坐骨神经运动神经、感觉神经阻滞持续时间,减少术后并发症的发生。     

Rhythm transformation in nerve fibers by local anesthetics: From biophysics of sodium channels to physiology of anesthesia

The review considers the basic stages in the study of rhythm transformation in the nerve fibers by local anesthetics and underlying use-dependent block of sodium channels. A potency of use-dependent local anesthetics to produce the rhythm transformation in nociceptive nerve fibers sufficient to attain local anesthesia without complete block of conduction was examined. A hypothesis was tested on attaining the conditions of local anesthesia by a decrease in discharge frequency of C-fiber nociceptors below the critical level separating the firing frequency in these sensors corresponding to their excitation with subnociceptive and nociceptive chemical stimuli. This critical level (about 2 Hz) was determined by comparison of the discharges in feline cutaneous C-fiber nociceptors during injection of chemical nociceptive and non-nociceptive stimuli. The discharge frequency in C-fiber nociceptors can be decreased in a use-dependent manner below the critical level by subcutaneous injection of lidocaine or N-propyl-ajmaline. The importance of use-dependent local anesthesia for preservation of trophic influences of the nervous system in the damaged tissue is discussed.     

Epidural Sustained Release Ropivacaine Prolongs Anti-Allodynia and Anti-Hyperalgesia in Developing and Established Neuropathic Pain

Ropivacaine is a local anesthetic widely used for regional anesthesia and epidural analgesia, but its relatively short duration limits its clinical use. A novel sustained release lipid formulation of ropivacaine has been recently developed to prolong its duration. We examined the epidural anti-hypersensitivity and preemptive effects of ropivacaine in mesylate injection and sustained release suspension forms in a rat model of neuropathy produced by peripheral nerve injury. Epidural administration of ropivacaine mesylate injection specifically blocked mechanical allodynia and thermal hyperalgesia by approximately 50% with a biological half-effective duration of approximately 3 hrs. The equivalent dose of ropivacaine free-base in sustained release suspension significantly prolonged the duration of anti-allodynia and anti-hyperalgesia by approximately 2 times. Multiple daily epidural injections of ropivacaine in both the mesylate injection and sustained-release suspension forms did not induce tolerance or potentiation to anti-allodynia or anti-hyperalgesia. Moreover, the single or multiple daily administration of ropivacaine mesylate injection before surgery in particular, markedly blocked the initiation and development of neuropathic pain, increasing the biological half-effective duration from less than 4 hrs up to 1 or 2 days. The single and multiple daily epidural injection of ropivacaine sustained release suspension further delayed the biological half-lives to 2 and 3 days, respectively. Our results indicate that the epidural administration of ropivacaine effectively blocks neuropathic pain without the induction of analgesic tolerance, and significantly delays the development of neuropathy produced by peripheral nerve injury. Epidural ropivacaine sustained release suspension produces much longer blockade effects of mechanical allodynia and heat hyperalgesia, and more significantly delays the development of neuropathic pain.     

Alterations of Na,K-ATPase Isoenzymes in the Rat Diabetic Neuropathy: Protective Effect of Dietary Supplementation with n-3 Fatty Acids

Abstract: Diabetic neuropathy is a degenerative complication of diabetes accompanied by an alteration of nerve conduction velocity (NCV) and Na,K-ATPase activity. The present study in rats was designed first to measure diabetes-induced abnormalities in Na,K-ATPase activity, isoenzyme expression, fatty acid content in sciatic nerve membranes, and NCV and second to assess the preventive ability of a fish oil-rich diet (rich in n-3 fatty acids) on these abnormalities. Diabetes was induced by intravenous streptozotocin injection. Diabetic animals (D) and nondiabetic control animals (C) were fed the standard rat chow either without supplementation or supplemented with either fish oil (DM, CM) or olive oil (DO, CO) at a daily dose of 0.5 g/kg by gavage during 8 weeks. Analysis of the fatty acid composition of purified sciatic nerve membranes from diabetic animals showed a decreased incorporation of C16:1(n-7) fatty acids and arachidonic acids. Fish oil supplementation changed the fatty acid content of sciatic nerve membranes, decreasing C18:2(n-6) fatty acids and preventing the decreases of arachidonic acids and C18:1(n-9) fatty acids. Protein expression of Na,K-ATPase α subunits, Na,K-ATPase activity, and ouabain affinity were assayed in purified sciatic nerve membranes from CO, DO, and DM. Na,K-ATPase activity was significantly lower in sciatic nerve membranes of diabetic rats and significantly restored in diabetic animals that received fish oil supplementation. Diabetes induced a specific decrease of α1- and α3-isoform activity and protein expression in sciatic nerve membranes. Fish oil supplementation restored partial activity and expression to varying degrees depending on the isoenzyme. These effects were associated with a significant beneficial effect on NCV. This study indicates that fish oil has beneficial effects on diabetes-induced alterations in sciatic nerve Na,K-ATPase activity and function.     

Activation of capsaicin receptors on the sciatic nerve induces FOS expression in the spinal dorsal horn of adult rats

By using immunohistochemical staining for FOS protein in the spinal cord, the role of capsaicin receptors on the sciatic nerve was investigated. After topical application of capsaicin (1%) to the sciatic nerve, FOS-like immunoreactive (FOS-LI) neurons were observed, chiefly in the superficial laminae of the lumbar dorsal horn. Topical application of capsazepine (5%) or lidocaine (2%) to the sciatic nerve for 15 min before the application of capsaicin reduced the number of FOS-LI neurons in the superficial dorsal horn (by 83.2 +/- 1.7 and 32.4 +/- 1.2%, respectively). One week after pretreatment of the sciatic nerve with colchicine, the number of FOS-LI neurons induced by capsaicin was greatly decreased (by 74.6 +/- 1.7%). Given that FOS protein expression after peripheral noxious stimulation is found in a location similar to that in the present study, our results indicate that the capsaicin receptor on the sciatic nerve is involved in the transmission of noxious information.     

Neutrophil leukocyte emigration induced by endotoxin. Mediator roles of interleukin 1 and tumor necrosis factor alpha 1

The hypothesis that cytokines mediate neutrophil emigration induced by endotoxin (LPS) was studied by examining the potency, the kinetics of neutrophil emigration, and the tachyphylaxis of intradermal sites with IL-1, TNF-alpha and LPS. Human rIL-1 alpha and IL-1 beta, synthetic lipid A, and LPS were several orders of magnitude more potent than human rTNF. The kinetic profiles of neutrophil emigration induced by IL-1 alpha, TNF, and LPS were characterized by minimal emigration in the first 30 min, followed by rapid and transient emigration. After the injection of LPS, the onset and the time at which the rate of emigration was maximal consistently appeared 30 min later than IL-alpha or TNF, suggesting that neutrophil emigration in response to LPS was mediated by a locally generated cytokine. IL-1 and TNF were then examined as potential secondary mediators of LPS-induced emigration by comparing the patterns of tachyphylaxis between LPS and IL-1 alpha or TNF; i.e., the magnitude of neutrophil emigration into inflammatory sites was compared with sites injected 6 h previously (desensitizing injections) with a cytokine or with LPS. Tachyphylaxis was dose dependent with each and also between the IL-1 species; therefore, when tachyphylaxis between the cytokines and LPS was examined, relatively higher doses were selected for the desensitizing injections than for the test injections. With this approach, desensitizing injections of IL-1 alpha diminished the neutrophil accumulation after LPS, and LPS also desensitized sites to IL-1 alpha. However, tachyphylaxis was not observed between TNF and LPS, or between TNF and IL-1 alpha. These data suggest that IL-1, but not TNF, is a potential mediator of LPS-induced neutrophil emigration.     

Characteristics of changes in lipids of granulation fibrous tissue of rats subjected to different doses and modes of melatonin administration

Melatonin influences the time-course of changes of lipids in granulation fibrous tissue in rats. Its effect depends on a dose, modes of administration (intraperitonial, subcutaneous or local) and duration of treatment. Intraperitonial administration of a single dose of melatonin (4 mg/kg) did not influence lipid content in the granulation fibrous tissue, while repeated injections of this hormone limited the increase in contents of lipids and phospholipids on the 5th and 8th days of regeneration. Long-term subcutaneous injections of melatonin caused distinct changes of lipids: at the dose of 0.3 mg/kg it prevented, and at the dose of 4 mg/kg it promoted the increase of lipid content in the granulation fibrous tissue on the fifth day of this study. Local application of melatonin solution (1.5 mg/ml) in early periods of regeneration caused insignificant changes of total lipids and total phospholipids in the granulation fibrous tissue. However, the higher concentration (15 mg/ml) of melatonin caused the decrease of total lipids due to reduced content of cholesterol and triglycerides and the increase of total phospholipids and some of their fractions.