BACKGROUND: Tissue injury by surgical manipulation or trauma may cause pain hypersensitivity secondary to central sensitization. The aim of this study was to evaluate the postoperative effect of gabapentin on incisional pain in rat pretreated with pentylenetetrazole. METHODS: Thirty rats were divided into 5 groups, a control group (n = 10), PTZ 10 group (n = 5), PTZ 20 group (n = 5), PTZ 30 group (n = 5), and a PG 30 group (n = 5). To evaluate postoperative mechanical hyperalgesia in injured feet, withdrawal thresholds were measured by calibrated von Frey filaments at 2 hr, 1 day, 2 days, 3 days, 4 days, and 5 days after the incision. RESULTS: The PTZ 10, 20, and 30 groups showed no significant difference in withdrawal thresholds when compared with the control group during 5 days postoperatively. There were no significant differences in withdrawal thresholds among the PTZ 10, 20, and 30 groups. However, the PG 30 group showed a significantly lower withdrawal threshold compared with the control group at postoperative days 3, 4 (p < 0.05), and 5 (p < 0.01). CONCLUSIONS: Intraperitoneal pentylenetetrazole administered before an incision had no effect on postoperative pain in the incisional pain model. However, gabapentin injection after an incision in rats pretreated with pentylenetetrazole caused hyperalgesia during 5 days postoperatively.
Animals ; Central Nervous System Sensitization ; Foot ; Hyperalgesia ; Hypersensitivity ; Pain, Postoperative ; Pentylenetetrazole* ; Rats*

Good pain control after surgery is important to facilitate overall recovery, improve patient satisfaction, decrease morbidity, and reduce health care cost. However, despite heightened awareness and development of new guidelines in recent decades, we have failed to make major improvements in postoperative pain control. Currently available analgesic therapies have limited efficacy, and pain after surgery continues to be a significant clinical problem. Our goal is to develop more effective and safer clinical strategies that will eliminate or greatly reduce postoperative pain, and a better understanding of the mechanisms of pain induced by surgery would be essential to achieve this goal. Evidence suggests that the pathophysiological mechanisms and optimal treatment of postoperative pain are different from many other painful conditions. Recognizing the necessity and importance of relevant pre-clinical models, we have developed and characterized rodent incision models that have close similarities to postoperative pain in patients. Previous studies have demonstrated the clinical relevance and translatability of these pre-clinical models of postoperative pain. In this review, we describe the rodent incision pain models, and summarized our current understanding of the mechanisms of postoperative pain, highlighting key findings from our previous studies using these models.
Central Nervous System Sensitization ; Health Care Costs ; Humans ; Pain, Postoperative* ; Patient Satisfaction ; Rodentia

BACKGROUND: Preemptive analgesia may improve postoperative antinociceptive treatment that prevents the development of central sensitization which contributes to post-injury pain hypersensitivity. However, beneficial effects of preemptive analgesia appear controversial. The purpose of this study was to examine the effect of pre- and post-incisional local infiltration of lidocaine and gabapentin on incisional pain in rats. METHODS: Thirty five male rats were divided into 7 groups; control group (n = 5), pre-lidocaine infiltration group (n = 5), post-lidocaine infiltration group (n = 5), pre-gabapentin 10 mg infiltration group (n = 5), post-gabapentin 10 mg infiltration group (n = 5), pre-gabapentin 30 mg infiltration group (n = 5), and post-gabapentin 30 mg infiltration group (n = 5). To evaluate postoperative mechanical hyperalgesia in injured feet, withdrawal thresholds were measured by calibrated von Frey filaments at 2 hrs, 1, 2, 3, 4, and 5 days after an incision. RESULTS: The pre-lidocaine infiltration group shows better analgesic effects than post-lidocaine infiltration group until postoperative day 1 (P < 0.05). The gabapentin infiltration groups were effective in postoperative pain management but there were no significant differences between pre- and post- incisional treatment. CONCLUSIONS: A preemptive lidocaine injection has a good analgesic effect on incisional pain. Gabapentin also has a good analgesic effect on incisional pain.
Analgesia ; Animals ; Central Nervous System Sensitization ; Foot ; Humans ; Hyperalgesia ; Hypersensitivity ; Lidocaine* ; Male ; Pain, Postoperative* ; Rats*

BACKGROUND: Reactive oxygen species (ROS) is known to be involved in chronic and persistent pain.By using the ROS scavenger 5,5-dimethyl-1-pyrroline N-oxide (DMPO), we studied the effects of ROS on formalin-induced nociception in rats. METHODS: 5% formalin was injected in the left hind paw after intraperitoneal injection of saline or various doses of DMPO (10 mg/kg, 30 mg/kg, 100 mg/kg).Number of flinches was measured in a 5 minute interval for 1 hour. RESULTS: Formalin injected into the left hind paw induced a biphasic nociceptive behaviour. Intraperitoneal injection of DMPO diminished nociceptive behaviors dose-dependently during phase 2 but not phase 1. CONCLUSIONS: ROS might be involved in central sensitization and DMPO, a ROS scavenger, posses antinociceptive property in rats subjected to formalin induced hyperalgesia.
Animals ; Central Nervous System Sensitization ; Formaldehyde ; Injections, Intraperitoneal ; Nociception ; Pain Measurement ; Rats ; Reactive Oxygen Species

BACKGROUND: A low dose of ketamine can be an effective preemptive analgesic by preventing central sensitization when administered before surgical trauma. In this study, we assessed the preemptive analgesic effect of low-dose ketamine administered intravenously to patients undergoing arthroscopic rotator cuff repair with intra articular ropivacaine injection. METHODS: This randomized, double-blinded study included fifty-six patients scheduled for elective arthroscopic rotator cuff repair. Normal saline (group C) or 0.5 mg/kg of ketamine (group K) was injected intravenously before the skin incision. An intra articular injection using 20 ml of 0.75% ropivacaine was performed in both groups just before wound closure by the surgeon at the end of the surgery. Postoperative pain was assessed by the numeric rating scale (NRS) in the post-anesthesia care unit (PACU) and at 12, 24, and 48 hours postoperatively. The total dose of fentanyl consumption and side effects were recorded. RESULTS: There were no significant differences between the C and K groups for the NRS of pain in the PACU and at 12, 24, and 48 hours after the surgery. In addition, there was also no significant difference in total fentanyl consumption between the two groups. CONCLUSIONS: Preemptive ketamine did not reduce preemptive pain scores and fentanyl consumption in patients who underwent arthroscopic rotator cuff repair with intra articular local anesthetic injection. Therefore, more aggressive and multimodal pain control is required in patients undergoing arthroscopic shoulder surgery regardless of the use of preemptive intravenous ketamine injection.
Central Nervous System Sensitization ; Fentanyl ; Humans ; Ketamine* ; Pain, Postoperative* ; Rotator Cuff* ; Shoulder ; Skin ; Wounds and Injuries

BACKGROUND: Preemptive analgesia is an antinociceptive treatment that prevents the development of central sensitization which contributes to the post-injury pain hypersensitivity. But controversies exist over the effectiveness and clinical value of preemptive analgesia. The aim of this study is to evaluate the preemptive effect of intrathecal bupivacaine on incisional pain in rats. METHODS: Thirty male rats were divided into 3 groups, saline-treated control group (n=10), post-treatment group (n=10), and pre-treatment group (n=10) according to the time which intrathecal administration of bupivacaine was done. To evaluate postoperative mechanical hyperalgesia in injured feet, withdrawal frequency and withdrawal thresholds were measured by von Frey filaments at 30 min, 1 hr, 2 hrs, 3 hrs, 1 day, 3 days and 7 days after incision. RESULTS: In control group, the withdrawal frequency increased from 0+/-0% before incision to 98.0+/-1.3% after the foot incision and the responses gradually declined during the postoperative 7 days to 52.0+/-4.7%. The median withdrawal threshold decreased from 148.43 mN before incision to 0.05 mN after foot incision and gradually increased during the postoperative 7 days to 6.79 mN. The post-treatment group showed no significant differences in the withdrawal frequency and withdrawal thresholds when compared with control group at post-operative 1 hour and thereafter (P<0.05). The pre-treatment group showed significantly lower withdrawal frequency and significantly higher withdrawal threshold compared with control group at postoperative 30 min and thereafter (P<0.05), and significantly lower withdrawal frequency and higher withdrawal threshold compared with post-treatment group at postoperative 2 hours and thereafter (P<0.05). CONCLUSION: We conclude that intrathecal bupivacaine administered before incision reduces postoperative delayed hyperalgesia in incisional pain model, and it may result from preventing the development of injury- induced central sensitization.
Analgesia ; Animals ; Bupivacaine* ; Central Nervous System Sensitization ; Foot ; Humans ; Hyperalgesia ; Hypersensitivity ; Male ; Pain, Postoperative* ; Rats*

BACKGROUND: Preemptive analgesia is an antinociceptive treatment that prevents the development of central sensitization which contributes to the post-injury pain hypersensitivity. But controversies exist over the effectiveness and clinical value of preemptive analgesia. The aim of this study is to evaluate the preemptive effect of intrathecal bupivacaine on incisional pain in rats. METHODS: Thirty male rats were divided into 3 groups, saline-treated control group (n=10), post-treatment group (n=10), and pre-treatment group (n=10) according to the time which intrathecal administration of bupivacaine was done. To evaluate postoperative mechanical hyperalgesia in injured feet, withdrawal frequency and withdrawal thresholds were measured by von Frey filaments at 30 min, 1 hr, 2 hrs, 3 hrs, 1 day, 3 days and 7 days after incision. RESULTS: In control group, the withdrawal frequency increased from 0+/-0% before incision to 98.0+/-1.3% after the foot incision and the responses gradually declined during the postoperative 7 days to 52.0+/-4.7%. The median withdrawal threshold decreased from 148.43 mN before incision to 0.05 mN after foot incision and gradually increased during the postoperative 7 days to 6.79 mN. The post-treatment group showed no significant differences in the withdrawal frequency and withdrawal thresholds when compared with control group at post-operative 1 hour and thereafter (P<0.05). The pre-treatment group showed significantly lower withdrawal frequency and significantly higher withdrawal threshold compared with control group at postoperative 30 min and thereafter (P<0.05), and significantly lower withdrawal frequency and higher withdrawal threshold compared with post-treatment group at postoperative 2 hours and thereafter (P<0.05). CONCLUSION: We conclude that intrathecal bupivacaine administered before incision reduces postoperative delayed hyperalgesia in incisional pain model, and it may result from preventing the development of injury- induced central sensitization.
Analgesia ; Animals ; Bupivacaine* ; Central Nervous System Sensitization ; Foot ; Humans ; Hyperalgesia ; Hypersensitivity ; Male ; Pain, Postoperative* ; Rats*

Tension-type headache is now the term used to describe headaches that have previously been grouped under various ill-defined headings, such as 'tension headache', 'stress headache' and 'muscle contraction headache'. Tension-type headaches are characterized by a pain that is mild to moderate in severity, bilateral in distribution, pressing or tightening in quality, and are not accompanied by major systemic disturbances or neurological signs. Tension-type headaches, the most prevalent from of headaches, are differentiated as being either episodic or chronic, Very little research on this disease has actually been carried out, and knowledge about key pathophysiological issues, such as the nature and site of the noxious stimulus, is limited. As a result of this and the lack of scientific interest for this from of headache in the medical field, the treatment is non-specific. However, it is suggested that a peripheral mechanism of tension-type headache be involved in the episodic form, whereas a secondary central sensitization and/or an impaired supraspinal modulation of incoming stimuli be involved in subjects with the chronic from. While most people with tension-type headaches experience mild, infrequent episodes, so that they do not regard the headache as a disease, a monority have chronic and often daily symptoms. The understanding of the balance between peripheral and central components in tension-type headache may lead us to a better prevention and treatment of this most prevalent type of headaches. This article presents a review on the drug therapy of tension-type headaches in adults.
Adult ; Central Nervous System Sensitization ; Drug Therapy* ; Head ; Headache ; Humans ; Tension-Type Headache*

Historically, peripheral neuropathic pain has occasionally been difficult to treat. Both a systematic review of the evidence as well as clinical experience have demonstrated that treatment options including polypharmacy provide effective pain relief in only half of the patients with neuropathic pain. After peripheral nerve injury, the incidence of degenerative alterations in the spinal cord and central pathologic sensitization are possible. Due to this observation, It may be difficult to treat this group of patients with peripheral neuropathic pain by therapeutic intervention of the peripheral nerve. Pulsed radiofrequency (PRF) has several benefits for treatment of this condition including, accuracy and safety, and the elimination of thermal lesions due to the reduction in the target tissue temperature (below 42 degrees). We treated three cases of supraorbital neuropathic pain using PRF, and discovered that two of the patients had significant pain relief at the six month time point.
Central Nervous System Sensitization ; Humans ; Incidence ; Neuralgia ; Peripheral Nerve Injuries ; Peripheral Nerves ; Peripheral Nervous System Diseases ; Polypharmacy ; Spinal Cord

Ketamine has been shown to have analgesic effect by blocking N-methyl-D-aspartate receptor, thus preventing and reducing central sensitization caused by peripheral nociceptive stimulation. However, due to lack of knowledge about its safety and toxicity in the central nervous system, either epidural or intrathecal injection of ketamine still remains controversial. Here, we describe a case report of satisfactory pain relief after the addition of ketamine in epidural injection in a patient with severe herpes zoster pain that was refractory to conventional medication, intravenous opioids and continuous epidural block. This case indicates the viability of epidural ketamine injection in patients with intractable herpetic neuralgia.
Analgesia, Epidural ; Analgesics, Opioid ; Central Nervous System ; Central Nervous System Sensitization ; Herpes Zoster ; Humans ; Injections, Epidural ; Injections, Spinal ; Ketamine* ; N-Methylaspartate ; Neuralgia*