• Clinics in Shoulder and Elbow
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• v.25 no.1
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• pp.73-89
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• 2022

Background: To evaluate the efficacy of autologous platelet-rich plasma (PRP) injections in the treatment of common shoulder diseases. Methods: The PubMed, Medline, and Central databases and trial registries were searched from their inception to October 2020 for randomized controlled trials of autologous PRP injections for shoulder diseases versus placebo or any control intervention. Preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were followed in the selection, analysis, and reporting of findings. The primary outcome was pain intensity (visual analog scale), and secondary outcomes were changes in function and quality of life (QoL). Results: A total of 17 randomized controlled trials of PRP versus control were analyzed. From 8-12 weeks to ≥1 year, PRP injections were associated with better pain relief and functional outcomes than control interventions. PRP injections were also associated with greater QoL, with an effect size of 2.61 (95% confidence interval, 2.01-14.17) at medium-term follow-up. Compared with placebo and corticosteroid injections, PRP injections provided better pain relief and functional improvement. In subgroup analyses, trials in which PRP was prepared by the double centrifugation technique, the platelet concentration in the PRP was enriched ≥5 times, leucocyte-rich PRP was used, or an activating agent was used before application reported the most effective pain relief at 6-7 months. Conclusions: PRP injections could provide better pain relief and functional outcomes than other treatments for persons presenting with common shoulder diseases. PRP injections have a greater capacity to improve shoulder-related QoL than other interventions.

• The Korean Journal of Pain
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• v.37 no.2
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• pp.141-150
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• 2024

Background: Stingless bee propolis is a popular traditional folk medicine and has been employed since ancient times. This study aimed to evaluate the antinociceptive activities of the chemical constituents of aqueous propolis extract (APE) collected by Trigona thoracica in a nociceptive model in mice. Methods: The identification of chemical constituents of APE was performed using high-performance liquid chromatography (HPLC). Ninety-six male Swiss mice were administered APE (400 mg/kg, 1,000 mg/kg, and 2,000 mg/kg) before developing nociceptive pain models. Then, the antinociceptive properties of each APE dose were evaluated in acetic acid-induced abdominal constriction, hot plate test, and formalin-induced paw licking test. Administration of normal saline, acetylsalicylic acid (ASA, 100 mg/kg, orally), and morphine (5 mg/kg, intraperitoneally) were used for the experiments. Results: HPLC revealed that the APE from Trigona thoracica contained p-coumaric acid (R² = 0.999) and caffeic acid (R² = 0.998). Although all APE dosages showed inhibition of acetic acid-induced abdominal constriction, only 2,000 mg/kg was comparable to the result of ASA (68.7% vs. 73.3%, respectively). In the hot plate test, only 2,000 mg/kg of APE increased the latency time significantly compared to the control. In the formalin test, the durations of paw licking were significantly reduced at early and late phases in all APE groups with a decrease from 45.1% to 53.3%. Conclusions: APE from Trigona thoracica, containing p-coumaric acid and caffeic acid, exhibited antinociceptive effects, which supports its potential use in targeting the prevention or reversal of central and peripheral sensitization that may produce clinical pain conditions.

• The Korean Journal of Pain
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• v.13 no.2
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• pp.143-148
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• 2000

Background: Trigeminovascular system is implicated in the pathophysiology of the headache in migraine. This study was designed to evaluate the pattern of Fos protein expression in trigeminal nociceptive central pathway after meningeal stimulation of rats by capsaicin. Methods: The expression of Fos protein was examined by immunohistochemistry in thalamus, brainstem and upper cervical cord (at three levels corresponding to obex, 0.8 mm and 2 mm below obex) 2 hours after intracisternal injection of either diluted capsaicin solution (0.1 ml, $61{\mu}g/ml$) or normal saline (0.1 ml) through a catheter placed in the cisterna magna, or following epidural instillation of diluted capsaicin solution in urethane-anesthetized Sprague-Dawley rats. Results: Fos immunoreactivity was strongly expressed within lamina I, II of bilateral trigeminal nucleus caudalis (TNC) after cisternal capsaicin injection and magnitude of expression was greatest at level 2.0 mm below obex. Epidural capsaicin caused much less labelling than cisternal capsaicin. Fos positive cells were also observed in area postrema, nucleus of the solitary tract, medullary reticular nucleus and midline nuclear groups of the thalamus with similar intensity between capsaicin and control group. Conclusions: These results indicate that the injection of capsaicin into the cisterna magna is an effective stimulus for the induction of Fos protein within TNC through activation of trigeminovascular afferents and this animal model can be useful for the evaluation of the pathophysiology and drug development in migraine and related headache.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.65-74
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• 2017

Here we investigated the central processing mechanisms of mechanical allodynia and found a direct excitatory link with low-threshold input to nociceptive neurons. Experiments were performed on male Sprague-Dawley rats weighing 230-280 g. Subcutaneous injection of interleukin 1 beta ($IL-1{\beta}$) ($1ng/10{\mu}L$) was used to produce mechanical allodynia and thermal hyperalgesia. Intracisternal administration of bicuculline, a gamma aminobutyric acid A ($GABA_A$) receptor antagonist, produced mechanical allodynia in the orofacial area under normal conditions. However, intracisternal administration of bicuculline (50 ng) produced a paradoxical anti-allodynic effect under inflammatory pain conditions. Pretreatment with resiniferatoxin (RTX), which depletes capsaicin receptor protein in primary afferent fibers, did not alter the paradoxical anti-allodynic effects produced by the intracisternal injection of bicuculline. Intracisternal injection of bumetanide, an Na-K-Cl cotransporter (NKCC 1) inhibitor, reversed the $IL-1{\beta}$-induced mechanical allodynia. In the control group, application of GABA ($100{\mu}M$) or muscimol ($3{\mu}M$) led to membrane hyperpolarization in gramicidin perforated current clamp mode. However, in some neurons, application of GABA or muscimol led to membrane depolarization in the $IL-1{\beta}$-treated rats. These results suggest that some large myelinated $A{\beta}$ fibers gain access to the nociceptive system and elicit pain sensation via $GABA_A$ receptors under inflammatory pain conditions.

• International Journal of Oral Biology
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• v.36 no.2
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• pp.43-50
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• 2011

Voltage dependent calcium channel (VDCC), one of the most important regulator of $Ca^{2+}$ concentration in neuron, play an essential role in the central processing of nociceptive information. The present study investigated the antinociceptive effects of L, T or N type VDCC blockers on the formalin-induced orofacial inflammatory pain. Experiments were carried out on adult male Sprague-Dawley rats weighing 220-280 g. Anesthetized rats were individually fixed on a stereotaxic frame and a polyethylene (PE) tube was implanted for intracisternal injection. After 72 hours, 5% formalin ($50 \;{\mu}L$) was applied subcutaneously to the vibrissa pad and nociceptive scratching behavior was recorded for nine successive 5 min intervals. VDCC blockers were administered intracisternally 20 minutes prior to subcutaneous injection of formalin into the orofacial area. The intracisternal administration of 350 or $700{\mu}g$ of verapamil, a blocker of L type VDCC, significantly decreased the number of scratches and duration in the behavioral responses produced by formalin injection. Intracisternal administration of 75 or $150 \;{\mu}g$ of mibefradil, a T type VDCC blocker, or 11 or $22\; {\mu}g$ of cilnidipine, a N type VDCC blocker, also produced significant suppression of the number of scratches and duration of scratching in the first and second phase. Neither intracisternal administration of all VDCC blockers nor vehicle did not affect in motor dysfunction. The present results suggest that central VDCCs play an important role in orofacial nociceptive transmission and a targeted inhibition of the VDCCs is a potentially important treatment approach for inflammatory pain originating in the orofacial area.

• International Journal of Oral Biology
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• v.43 no.3
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• pp.147-153
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• 2018

The aim of the present study was to evaluate the central antinociceptive effects of eugenol after intraperitoneal administration. Experiments were carried out using male Sprague-Dawley rats. Subcutaneous injection of 5% formalin-induced nociceptive behavioral responses was used as the pain model. Subcutaneous injection of 5% formalin significantly produced nociceptive responses by increasing the licking time during nociceptive behavior. Subsequent intraperitoneal injection of 100 mg/kg of eugenol led to a significant decrease in the licking time. However, low dose of eugenol (50 mg/kg) did not affect the nociceptive behavioral responses produced by subcutaneous injection of formalin. Intrathecal injection of $30{\mu}g$ of naloxone, an opioid receptor antagonist, significantly blocked antinociceptive effects produced by intraperitoneal injection of eugenol. Neither intrathecal injection of methysergide ($30{\mu}g$), a serotonin receptor antagonist nor phentolamine ($30{\mu}g$), an ${\alpha}-adrenergic$ receptor antagonist influenced antinociceptive effects of eugenol, as compared to the vehicle treatment. These results suggest that central opioid pathway participates in mediating the antinociceptive effects of eugenol.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.3
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• pp.307-312
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• 1998

This study was performed to investigate the mechanism of central analgesic effects of antidepressants. Thirty four male rats were anesthetized with pentobarbital sodium (40 mg/kg, ip). A stainless steel guide cannula and a PE tube (PE10) were implanted into the lateral ventricle and cisterna magna area. Stimulating and recording electrodes were implanted into the incisor pulp and anterior digastric muscle. Electrodes were led subcutaneously to the miniature cranial connector sealed on the top of the skull with acrylic resin. The jaw opening reflex was used in freely moving rats, and antidepressants were administered intracisternally in order to eliminate the effects of anesthetic agents on the pain assessment and evaluate the importance of the central action site of antidepressants. After 48 hours of recovery from surgery, digastric electromyogram (dEMG) of freely moving rats was recorded. Electrical shocks (200 ${\mu}sec$ duration, 0.5-2 mA intensity) were delivered at 0.5 Hz to the dental pulp every 2 minute. Intracisternal administration of $15\;{\mu}g$ imipramine suppressed dEMG elicited by noxious electrical stimulation in the tooth pulp to $76{\pm}6%$ control. Intracisternal administration of $30\;{\mu}g$ desipramine, nortriptyline, or imipramine suppressed dEMG remarkably to $48{\pm}2,\;27{\pm}8,\;or\;25{\pm}5%$ of the control, respectively. Naloxone, methysergide, and phentolamine blocked the suppression of dEMG produced by intracisternal antidepressants from $23{\pm}2\;to\;69{\pm}4%,\;from\;32{\pm}5\;to\;80{\pm}9%,\;and\;from\;24{\pm}6\;to\;77{\pm}5%$ of the control, respectively. These results indicate that antidepressants produce antinociception through central mechanisms in the orofacial area. Antinociception of intracisternal antidepressants seems to be mediated by an augmentation of descending pain inhibitory influences on nociceptive pathways.

• The Journal of Korean Medicine
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• v.40 no.2
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• pp.119-132
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• 2019

Purpose: This study was conducted to collect and analyze real world data to evaluate the effectiveness and safety of comprehensive traditional Korean Medicine treatment on quality of life, anorexia and cachexia of cancer patients. Methods: We analyzed medical records of 62 cancer patients admitted to O-I Dang Korean Medicine Hospital from February 2018 to February 2019. The primary outcome was a change score in the Anorexia/Cachexia Subscale of Functional Assessment of Anorexia/Cachexia Therapy (FAACT). The secondary outcomes were Functional Assessment of Cancer Therapy-General (FACT-G), Trial Outcome Index(TOI) of FAACT, 11 point Pain Intensity Numeric Rating Score (11 PI-NRS) and Patient Global Impression of Change (PGIC) and adverse event. Results: Cachexia and quality of life in cancer patients assessed by FAACT, increased by $5.59{\pm}14.83$ (p=0.004) after treatment. PI-NRS was reduced by $2.10{\pm}1.81$ (p<0.001) and TOI and FACT-G total scores were increased by $5.17{\pm}11.70$ (p=0.001) and $3.59{\pm}10.94$ (p=0.012), respectively. These results were also clinically meaningful assessed via minimal clinically important difference (MCID). There was no severe adverse event. Conclusion: These findings suggest that comprehensive traditional Korean Medicine treatment might be effective and safe strategy for improving quality of life, anorexia, cachexia and pain of cancer patients. Further advanced studies with controlled group and more participants with rigorous design are needed to ensure these findings.

• Journal of Korean Neurosurgical Society
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• v.54 no.4
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• pp.359-362
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• 2013

Chronic hypoventilation due to injury to the brain stem respiratory center or high cervical cord (above the C3 level) can result in dependence to prolonged mechanical ventilation with tracheostomy, frequent nosocomial pneumonia, and prolonged hospitalization. Diaphragm pacing through electrical stimulation of the phrenic nerve is an established treatment for central hypoventilation syndrome. We performed chronic phrenic nerve stimulation for diaphragm pacing with the spinal cord stimulator for pain control in a quadriplegic patient with central apnea due to complete spinal cord injury at the level of C2 from cervical epidural hematoma. After diaphragmatic pacing, the patient who was completely dependent on the mechanical ventilator could ambulate up to three hours every day without aid of mechanical ventilation during the 12 months of follow-up. Diaphragm pacing through unilateral phrenic nerve stimulation with spinal cord stimulator was feasible in an apneic patient with complete quadriplegia who was completely dependent on mechanical ventilation. Diaphragm pacing with the spinal cord stimulator is feasible and effective for the treatment of the central hypoventilation syndrome.

• Journal of Acupuncture Research
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• v.15 no.2
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• pp.301-310
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• 1998

Infrared thermographic imaging visualizes noninvasively various abnormal condition by detecting the skin temperature. As the imaging represents the objective condition by the changes in blood flow under the control of autonomic nervous system, it is used to diagnosis and monitor the lumboscral radiculopathy. And asymmetry is important in the diagnosis of disc herniation. The most common type of disc herniation occurs psoterolaterally. This frequently causes nerve root compression leading to a radiculopathy in the distribution of the involved nerve root, most of which also provoke the asymmetric changes in thermography. Central disc herniation, which accounts for 5% to 35% of disc herniation, is typically associated with low back pain. But radiculopathy is usually abscent unless central disc heriniaton is large enough to cause compression of the cauda equina. To evalute the diagnostic value of the thermographic imaging in the diagnosis of central disc herniation, the imaging of 15 normal subjects and 48 patients with central disc herniation documented by CT scan were analyzed. The patients had either bilateral radiculophathy or no radiculopathy. The imaging of patient group with non rediculopathy did not show any significant thermal difference to control. While bilateral radiculopathy group reveled hypothermic pattern compared twith control. Thermal difference between left and right side did not present any significance in non radiculopathy group but hypothermia in bilateral radiculopathy group. Large herniation group demonstrated hyperthemic pattern while the others showed no significant change. Cranial caudal thermal difference did not show any difference between experiment groups. These results shows that infrared thermographic imaging can be used central disc herniation with bilateral radiculopathy, while it seems to little useful on the diagnosis of non radiculopathic disc herniation.