In the second chapter, I proved that stimulation of an acupuncture point with Scolopendra subspinipes (pharmacopuncture with Scolopendra subspinipes, SSP) causes an analgesic effect via alpha2-adrenoreceptors in the spinal cord. Therefore, SSP produces an analgesic effect by activating the descending inhibitory system for pain, indicating the possibility of pain management.
Local analgesics
Pharmacopuncture
Time-restricted feeding
The ascending pain pathway consists of three neural pathways (1st, 2nd, and 3rd order neurons) (C) The ascending pain pathway is divided into a lateral and medial pathway. The lateral pathway is responsible for the perception of painful sensation and for identifying the location of the painful stimulus.
PURPOSE
The analgesic effect of sinomenine via inhibition of voltage-gated
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
Free-floating sections were washed with 0.01 M PBS and incubated in 0.3% H O (in distilled water) for 30 min at room temperature (RT). After elimination of endogenous peroxidase, the sections were washed with 0.01 M PBS and pre-blocked with 5% normal goat serum (NGS) in PBS with 0.3% triton x (PBST) for 1 hour at room temperature.
RESULTS
I next examined the effects of sinomenine on the excitability of small DRG neurons (<20 μm diameter). Because the VGSCs are responsible for the generation of the APs, I tested the effect of sinomenine on INa in small DRG neurons using a command pulse stepwise from -90 to -10 mV. These results suggest peripheral action of sinomenine on VGSCs in nociceptive neurons, which may be associated with sinomenine's analgesic effect on acute inflammatory pain.
Intraplantar application of sinomenine on formalin-induced pain behavior To elucidate the peripheral effect of sinomenine, I next investigated whether peripheral injection of sinomenine actually produces analgesic effects. Because drug-induced motor impairment can result in false positives in nociceptive pain behavior, I performed rota-rod testing to examine the effect of sinomenine on motor function. Intraperitoneal (i.p.) injection of sinomenine inhibited formalin-induced pain behavior in both the first phase and the second phase at a dose of 50 mg/kg or 75 mg/kg.
Effects of sinomenine on voltage-gated sodium channel in small dorsal root ganglion neurons.
DISCUSSION
After the noxious stimulation, primary afferent nociceptive neurons (Aδ and C fiber) transmit the pain signal to second-order neurons in the superficial dorsal horn of the spinal cord. For example, c-Fos are expressed in the superficial dorsal horn of the spinal cord following noxious stimulation46 and the reduction of c-Fos expression is often used to demonstrate peripheral analgesic effects43. In this study, I found that sinomenine (50 mg/kg i.p.) decreased formalin-induced c-Fos expression in the superficial dorsal horn.
In this study, I observed that sinomenine was effective at a concentration range of ~mM on cellular excitability and VGSCs in small DRG neurons. However, I have observed motor dysfunction and some sedative effect with high dose sinomenine (75 mg/kg i.p.). Because systemic administration of sinomenine at high doses has side effects such as sedation, gastrointestinal and renal damage, it is important to use sinomenine in low concentrations.
In the present study, I found that i.pl administration of sinomenine shows analgesic effect at low concentration which showed no analgesic effect when administered systemically (20 ~ 25 mg/kg i.pl vs. 25 mg/kg i.p.), implying use of therapeutic potential as a local analgesic in the periphery.
Pharmacopuncture with
Pharmacopuncture is a new form of acupuncture therapy that combines acupuncture with herbal medicine by injecting herbal extract into the acupuncture point and has been reported to be more effective than acupuncture alone. It is located in the lateral knee joint, 5 mm lateral to the anterior tubercle of the tibia. 10 min after SSP, 20 μl of 1% formalin was subcutaneously injected into the plantar surface of the right hind paw.
A reflex movement of the tail indicated successful insertion of the needle into the subarachnoid space. Again, bilateral treatment of SSP also had no significant effect on formalin-induced spontaneous pain behavior (Fig. 11B). Activation of the peripheral nerves of the specific acupoint is essential for the analgesic effect of SSP in oxaliplatin-induced mechanical allodynia.
Injection of SS at non-acupuncture sites did not affect the oxaliplatin-induced decrease in PWT (Figure 13B).
Peripheral nerve activation of the specific acupoint is associated with Scolopendra subspinipes pharmacopuncture (SSP)-induced anti-allodynia. A) Effect of subcutaneous pretreatment with lidocaine on pharmacopuncture with Scolopendra subspinipes (SSP)-induced anti-allodynic effect in oxaliplatin (OXA)-treated mice. Compared to subcutaneous (s.c.) injection of vehicle (20% ethanol) with SSP (vehicle + SSP), which induced anti-allodynia, pretreatment with lidocaine (0.5%/20 μl, s.c.) in the ST36 acupoint ( lidocaine + SSP) 10 minutes before SSP reversed SSP-induced anti-allodynia. Lidocaine alone (lidocaine + saline) did not affect OXA-induced mechanical allodynia (vehicle + saline). B) SSP reversed oxaliplatin-induced mechanical allodynia with the bilateral ST36 acupoint injection, but did not affect PWT with SSP at a non-acupoint location (back or buttocks).
Therefore, the analgesic effect of SSP may not be due to a systemic effect of SS. Therefore, it is likely that SSP-induced analgesia at ST36 is not mediated solely by a simple pharmacological effect of nerve agents, particularly in the peroneal nerve. These findings suggest that the analgesic effect of SSP on oxaliplatin-induced neuropathy may be related to the activation of peripheral neurons in the ST36 acuity.
With this in mind, I assessed whether the anti-allodynic effect of SSP is mediated by the descending endogenous pain inhibitory system coupled to the spinal alpha2-adrenergic, opioidergic and/or serotonergic system. This result indicates that spinal alpha2-adrenoceptors, but not opioid or serotonin receptors, are involved in the analgesic effect of SSP. Although this study shows a potential therapeutic effect of SSP on oxaliplatin-induced established pain, prevention of chemotherapy-induced pain is also clinically important.
Further research is needed to evaluate the effect of SSP on the development of chemotherapy-induced neuropathic pain.
Both acute fasting and refeeding alleviate inflammatory pain but via
In the formalin-induced acute inflammatory pain model, fasting suppressed pain behavior only in the second phase and the analgesic effect was also observed after refeeding. Consistent with previous studies, acute fasting suppressed formalin-induced spontaneous pain behavior with a significant analgesic effect only in the second phase (Fig. 15A). Compared with the freely fed group, the 2 hour fed group had a significant analgesic effect only in the second phase, and this analgesic effect disappeared after 24 hours of refeeding (Fig. 15A).
These results suggest that both fasting and refeeding produce an analgesic effect on acute inflammatory pain but did not affect non-inflammatory pain (nociception). In the formalin-induced acute pain model, both calorie-free agar refeeding and normal laboratory chow had an analgesic effect only in the second phase (Fig. An additional analgesic effect from calorie-free agar refeeding suggests that the satiety signal consisting from caloric recovery and gastric distension may have interfered with refeeding-induced analgesia.
Taken together, these findings suggest that caloric recovery after fasting may serve as an additional factor for rebirth-induced analgesic efficacy.
I confirmed that fasting and refeeding produce an analgesic effect via different mechanisms, with fasting producing an analgesic effect via the opioid and endocannabinoid systems, but these systems are not involved in refeeding-induced analgesia. Both refeeding of non-calorie agar and calorie recovery by D-glucose injection (i.p.) after fasting had an additive analgesic effect, compared with fasting-induced analgesia. In the current study, I found that acute fasting leads to analgesic effects in acute inflammatory pain via the opioid and cannabinoid systems, while the analgesic effect of refeeding was not associated with this.
In the present study, glucose administration (i.p.) was found to have a greater analgesic effect compared to fasting alone, while blood glucose levels remained high (Fig. 18), suggesting that refeeding-induced analgesia is also associated with a caloric recovery. Therefore, refeeding-induced analgesia consists of multiple phenomena that occur simultaneously and are clearly distinguished from simple fasting-induced analgesia. Therefore, it is possible that the affective component of pain resulting from significant gastric distension may interfere with refeeding-induced analgesia.
Therefore, fullness due to gastric distension may interfere with the analgesic effect of refeeding in formalin test by activating PBN (Fig. 17C and D).
CONCLUSION
포르말린 시험에서 전압 활성화 Na+ 채널 차단제의 항통각 효과 비교. 통증에는 감각적 요소와 정서적 요소가 모두 있기 때문에 기존의 약리학적 접근법(NSAID 및 오피오이드)만으로는 통증을 효과적으로 조절하기가 어렵습니다. 따라서 통증 관리에 대한 다각적인 접근 방식을 탐구하기 위해 이 논문에서는 주로 국소 진통제(sinomenine), 약초(Scolopendra subspinipes, Wukong 약초) 및 시간 제한 수유(단식/단식 후)의 통증 관리 잠재력을 조사합니다. 보충수유)가 연구의 주제였습니다.
시노메닌의 복강내 투여는 포르말린 유발 통증 행동을 유의하게 감소시켰으며 c-. 오공약침을 족삼리 부위에 피하 투여하면 옥살리플라틴 치료로 인한 신경병증성 통증이 감소되고, 알파2-아드레날린 수용체 길항제로 알려진 요힘빈을 척수에 주사하면 통증이 유발되는 것으로 확인되었습니다. 안도. 오공약침으로 발견한 효과가 억제됩니다. 따라서 오공약침에 의한 경혈점의 자극은 하행통증억제체계를 활성화시키고 진통효과를 나타내어 오공약침을 통한 통증관리의 가능성을 시사한다.
24시간 단식으로 유발된 통증 억제 효과는 엔도카나비노이드 및 오피오이드 시스템과 관련이 있는 반면, 2시간 재급식으로 유발된 진통 반응은 식습관 자체와 칼로리 회복과 관련이 있습니다.
