ABSTRACT
The incidences of systemic toxicity and other complications associated with existing local anaesthetics can occur at clinical concentration level and vary with the anaesthetic techniques, types of surgery and patient factors. This evidence suggests the need for therapeutic interventions in peripheral and regional anaesthesia. Buthus martensii Karsch (BmK) scorpion venom is a compound that contains mixtures of peptides that have analgesic properties. This study aimed to investigate the local anaesthetic activity of scorpion venom peptide, AGAP (analgesic-antitumor peptide) in mechanical hyperalgesia or acute inflammatory pain. Method: Formalin was injected into the left hind paw after 20 minutes of infiltration of drugs. The time of licking or flinching of the injected hind paw was recorded as indicative of nociceptive or acute inflammatory pain. Paw flinching or quick withdrawal was considered a positive response to pain in the partial sciatic nerve ligation. The paw-withdrawal threshold (PWT) was determined by consecutively increasing and decreasing the magnitude of the stimulus. Results: The results indicated that AGAP exhibited a 67.9% inhibition in licking or flinching time and an 88.1% inhibition in paw withdrawal in mechanical hyperalgesia. The addition of AGAP to lidocaine showed an 89.5% inhibition in paw withdrawal. Conclusion: The data presented in this study suggest that local infiltration of AGAP significantly reduced mechanical hyperalgesia and acute inflammatory pain
Subject(s)
Humans , Scorpions , Nociceptive Pain , Scorpion Venoms , Acute Pain , Anesthetics, LocalABSTRACT
Objective@#To investigate the morphological changes in microglia and astroglia before and after the removal of occlusal interferences in rats and to further understand whether astroglia and microglia activation is involved in experimental occlusal interference-induced masticatory muscle pain.@*Methods@#Male Sprague-Dawley rats (200-220 g) were used. Crowns of two heights (0.2 mm and 0.4 mm) were bonded to the right maxillary first molars to establish experimental rat models of occlusal interference. The rats were randomly assigned to one of five groups of twelve rats each: sham-occlusal interference control group, 0.4 mm occlusal interference group, 6-day removal of 0.4 mm occlusal interference group, 0.2 mm occlusal interference group, and 6-day removal of 0.2 mm occlusal interference group. The rats were sacrificed by transcardiac perfusion after deep anesthetization on days 3, 5, 7, and 14. Brain stem sections were obtained and processed for immunofluorescence staining of GFAP and OX-42. Expression levels were semiquantitatively analyzed.@*Results@#① Based on the markers OX-42 and GFAP, trigeminal-spinal nucleus (Vsp) microglia and astroglia showed no activation in the sham-occlusal interference control group. ② In the 0.4 mm and 0.2 mm occlusal interference groups, Vsp microglia and astroglia showed mild to moderate activation after 3-7 days of occlusal interference. Vsp astroglia remained activated on day 14, but Vsp microglia did not. At the same time point, the 0.4 mm occlusal interference group had greater activation than the 0.2 mm occlusal interference group. ③ In the 6-day removal of 0.4 mm and 0.2 mm occlusal interference groups, microglia and astroglia activation decreased after removal of the occlusal interference. Vsp astroglia remained activated on day 14, but microglia showed no activation.@*Conclusion@#Microglia and astrocyte activation is induced in the Vsp after experimental occlusal interference. The astrocytes remained activated for longer than the microglia. The glia activation level is closely related to the intensity of occlusal interference.
ABSTRACT
Objective@#To investigate the morphological changes in microglia and astroglia before and after the removal of occlusal interferences in rats and to further understand whether astroglia and microglia activation is involved in experimental occlusal interference-induced masticatory muscle pain.@*Methods@#Male Sprague-Dawley rats (200-220 g) were used. Crowns of two heights (0.2 mm and 0.4 mm) were bonded to the right maxillary first molars to establish experimental rat models of occlusal interference. The rats were randomly assigned to one of five groups of twelve rats each: sham-occlusal interference control group, 0.4 mm occlusal interference group, 6-day removal of 0.4 mm occlusal interference group, 0.2 mm occlusal interference group, and 6-day removal of 0.2 mm occlusal interference group. The rats were sacrificed by transcardiac perfusion after deep anesthetization on days 3, 5, 7, and 14. Brain stem sections were obtained and processed for immunofluorescence staining of GFAP and OX-42. Expression levels were semiquantitatively analyzed.@*Results@#① Based on the markers OX-42 and GFAP, trigeminal-spinal nucleus (Vsp) microglia and astroglia showed no activation in the sham-occlusal interference control group. ② In the 0.4 mm and 0.2 mm occlusal interference groups, Vsp microglia and astroglia showed mild to moderate activation after 3-7 days of occlusal interference. Vsp astroglia remained activated on day 14, but Vsp microglia did not. At the same time point, the 0.4 mm occlusal interference group had greater activation than the 0.2 mm occlusal interference group. ③ In the 6-day removal of 0.4 mm and 0.2 mm occlusal interference groups, microglia and astroglia activation decreased after removal of the occlusal interference. Vsp astroglia remained activated on day 14, but microglia showed no activation.@*Conclusion@#Microglia and astrocyte activation is induced in the Vsp after experimental occlusal interference. The astrocytes remained activated for longer than the microglia. The glia activation level is closely related to the intensity of occlusal interference.
ABSTRACT
Objective To investigate the effects of dehydrocorydaline(DHC) on complete Freund's adjuvant (CFA)-induced mechanical hyperalgesia in mice.Methods 40 mice were divided randomly into 4 groups (CFA test:experiment group =8,control group =8;locomotor activity and organ coefficient test:experiment group=12,control group =12).Subcutaneously injected CFA in the plantar of mice to establish pain model.The experimental group mice were injected with 10 mg/kg DHC while the control group mice received 10％ DMSO.The paw withdrawal mechanical threshold(PWMT) of mice was tested before and after administration of DHC.The effects of DHC on spontaneous activity and organ coefficient were observed in mice.Results The basic values of PWMT showed there were no statistically significant differences between experimental group and control group ((10.27± 1.34)g vs (10.28 ±0.35)g,P＞0.05).Compared with the control group,the values of PWMT in experimental group at 0.5 h,1 h,2 h,3 h after administration of DHC were significantly increased(0.5 h:(8.18±0.87) g vs (4.85±0.65) g;1 h:(7.85±0.59) g vs (4.84±0.54) g;2 h:(7.36±0.49) g vs (4.90±0.59) g;3 h:(6.66±0.45) g vs (5.00±0.36) g;all P＜0.01).Compared with the control group,no significant effect was observed on the number mice crossed grids and lifted forelimb and stood in 2 min in the experimental group (P＞ 0.05).And no significant effect was observed on the liver,kidney,spleen,heart,lung and brain organ coefficient in the experiment group (P＞0.05).Conclusion DHC can alleviate CFA-induced mechanical hyperalgesia in mice.
ABSTRACT
Muscular unmyelinated (C-) fibers are supposed to be the afferent limb of acupuncture effects. Of muscular unmyelinated afferent receptors, polymodal receptors are considered to be important because of their sensitivities to moderate mechanical and strong thermal stimulations and to algesic substances. I would like to introduce response characteristics of muscular polymodal receptors, especially on their sensitization to mechanical stimulation.Polymodal receptors consist of 50% of mechano-sensitive muscular C-fiber receptors in rats. Comparing with non-polymodal receptors that would not respond to heat stimulation, the mechanical threshold of the polymodals is not different, but their discharge rate is lower. The response threshold to heat is around 41°C. The mechanical response of this receptor is augmented by bradykinin, prostaglandins, histamine and acid. Nerve growth factor (NGF) is one of neurotrophic factors that is essential for the development and survival of thin-fiber afferents and their differentiation during ontogeny. In adulthood NGF is produced in inflammatory cells (macrophages, mast cells, etc) and fibroblasts, and sensitizes nociceptors to heat and mechanical stimulations, and plays an important role in hyperalgesia. It is reported that intramuscular injection of NGF into humans induced mechanical hyperalgesia.Recently we found up-regulation of NGF in the muscle in non-inflammatory condition, namely in delayed onset muscle soreness that appears after strenuous and unaccustomed exercise (delayed onset muscle soreness). Up-regulation of NGF in the muscle starts about 12 hrs after exercise, and it lasts up to 2 days after exercise. Anti-NGF antibody injection to the muscle on the 2nd day after exercise, reversed mechanical hyperalgesia. Thus it is concluded that sensitization of C-fiber receptors by NGF to mechanical stimulation results in mechanical hyperalgesia. Because there is no sign of inflammation in the muscle, cells that produce NGF cannot be inflammatory cells, and muscle cells themselves, blood vessel cells or connective tissue cells might produce NGF. In addition, the majority of sensory receptors that are sensitized after exercise are heat sensitive, that means they are mostly polymodal receptors. Because many of muscle pain conditions are not inflammatory, non-inflammatory production of NGF in the muscle observed in the delayed onset muscle soreness raises a possibility that NGF is produced in other muscle pain conditions, and sensitizes muscle nociceptors to result in muscle hyperalgesia. This point must be clarified in future.
ABSTRACT
Objective To investigate the effect of intraperitoneal injection of thalidomide on pain behaviors in a mouse model of bone cancer pain. Methods 36 male C3H/HeJ mice were divided randomly into tumor group (n= 18) and sham group (n= 18) ,six mice from each group were chosen to examine the time course of changes in behavior after tumor cells inoculated to the bone. 2 × 105 osteosarcoma NCTC 2472 cells were implanted into the intramedullary space of the right femurs of mice to induce ongoing bone cancer related pain behaviors. The sham group was inoculated by α-MEM without any cells. On the day before inoculation,the tumor mice were divided randomly into tumor + thalidomide group and tumor + vehicle group. The sham group mice were further divided randomly into sham + thalidomide group and sham + vehicle group. Pain ethology indexes such as paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were observed on 1 d before inoculation and on 3 d ,5 d ,7 d, 10 d, 14 d after inoculation. Results ( 1 ) At day 7 after the operation, compared with sham mice ( 1. 70 ± 0. 33 ) g, PWMT of tumor mice decreased to ( 1.07 ± 0. 30) g (P ＜ 0. 05 ). At day 10, PWTL shortened to ( 12.60 ± 1.69 ) s (P ＜ 0. 05 ) compared with sham mice ( 17.70 ± 1.54 ) s. And the pain behaviors of tumor mice were aggravated along with the development of cancer pain. (2) At day 7 after the operation, compared with tumor + vehicle group ( 1. 07 ± 0.39 ) g, PWMT of tumor + thalidomide group increased to ( 1. 53 ± 0. 39 ) g (P ＜0.05). At day 10, PWTL extended to ( 16.48 ± 1.13 ) s compared with sham mice ( 12.64 ± 1. 56) s (P ＜0. 05 ). Conclusion Intraperitoneal injection of thalidomide can efficiently relieve mechanical hyperalgia and thermal hyperalgia in a mouse model of bone cancer pain.
ABSTRACT
Since streptozotocin (STZ)-induced diabetes is a widely used model of painful diabetic neuropathy, the aim of the present study was to design a rational protocol to investigate whether the development of mechanical hypernociception induced by STZ depends exclusively on hyperglycemia. Male Wistar rats (180-200 g; N = 6-7 per group) received a single intravenous injection of STZ at three different doses (10, 20, or 40 mg/kg). Only the higher dose (40 mg/kg) induced a significant increase in blood glucose levels, glucose tolerance and deficiency in weight gain. However, all STZ-treated rats (hyperglycemic or not) developed persistent (for at least 20 days) and indistinguishable bilateral mechanical hypernociception that was not prevented by daily insulin treatment (2 IU twice a day, sc). Systemic morphine (2 mg/kg) but not local (intraplantar) morphine treatment (8 µg/paw) significantly inhibited the mechanical hypernociception induced by STZ (10 or 40 mg/kg). In addition, intraplantar injection of STZ at doses that did not cause hyperglycemia (30, 100 or 300 µg/paw) induced ipsilateral mechanical hypernociception for at least 8 h that was inhibited by local and systemic morphine treatment (8 µg/paw or 2 mg/kg, respectively), but not by dexamethasone (1 mg/kg, sc). The results of this study demonstrate that systemic administration of STZ induces mechanical hypernociception that does not depend on hyperglycemia and intraplantar STZ induces mechanical sensitization of primary sensory neurons responsive to local morphine treatment.
Subject(s)
Animals , Male , Rats , Hyperalgesia/chemically induced , Hyperglycemia/chemically induced , Mechanoreceptors/drug effects , Nociceptors/drug effects , Peripheral Nerves/drug effects , Streptozocin/administration & dosage , Analgesics, Opioid/therapeutic use , Dose-Response Relationship, Drug , Glucose Tolerance Test , Hyperalgesia/drug therapy , Hyperalgesia/physiopathology , Hyperglycemia/physiopathology , Mechanoreceptors/physiology , Morphine/therapeutic use , Nociceptors/physiology , Pain Measurement , Peripheral Nerves/physiopathology , Rats, WistarABSTRACT
BACKGROUND: This study was conducted to investigate the roles of the spinal and peripheral gamma-aminobutyric acid (GABA)-ergic systems for the mechanical hypersensitivity produced by chronic compression of the dorsal root ganglion (CCD). METHODS: CCD was performed at the left 5th lumbar dorsal root ganglion. The paw withdrawal threshold (PWT) to von Frey stimuli was measured. The mechanical responsiveness of the lumbar dorsal horn neurons was examined. GABAergic drugs were delivered with intrathecal (i.t.) or intraplantar (i.pl.) injection or by topical application onto the spinal cord. RESULTS: CCD produced mechanical hypersensitivity, which was evidenced by the decrease of the PWT, and it lasting for 10 weeks. For the rats showing mechanical hypersensitivity, the mechanical responsiveness of the lumbar dorsal horn neurons was enhanced. A similar increase was observed with the normal lumbar dorsal horn neurons when the GABA-A receptor antagonist bicuculline was topically applied. An i.t. injection of GABA-A or GABA-B receptor agonist, muscimol or baclofen, alleviated the CCD-induced hypersensitivity. Topical application of same drugs attenuated the CCD-induced enhanced mechanical responsiveness of the lumbar dorsal horn neurons. CCD-induced hypersensitivity was also improved by low-dose muscimol applied (i.pl.) into the affected hind paw, whereas no effects could be observed with high-dose muscimol or baclofen. CONCLUSIONS: The results suggest that the neuropathic pain associated with compression of the dorsal root ganglion is caused by hyperexcitability of the dorsal horn neurons due to a loss of spinal GABAergic inhibition. Peripheral application of low-dose GABA-A receptor agonist can be useful to treat this pain.