• Korean Journal of Psychosomatic Medicine
• /
• v.8 no.1
• /
• pp.65-71
• /
• 2000

Objects : Aimed to test the hypothesis that neonatal testosterone exposure in female mice influences the development of testosterone-related pain inhibitory system and that testosterone administered in adulthood decreases the pain sensitivity. Methods : Thirty androgenized(testosterone propionate $100{\mu}g$ ip within 24 hrs after birth) adult female and twenty five control(normal saline $100{\mu}g$ ip within 24 hrs after birth) adult female mice were injected with testosterone propionate 1mg/kg/day for 3 consecutive days from 84th experimental days. Nociceptive sensitivity was measured before and after treatment of testosterone by tail flick latency on 84th and 86th experimental days. Results : 1) On the 84th experimental day, basal nociceptive sensitivity was significantly higher in the androgenized group($2.7{\pm}0.4$ sec) as compared to the control group($3.3{\pm}1.1$ sec). 2) Testosterone treatment on the 84th experimental day significantly lowered nociceptive sensitivity in both androgenized($5.2{\pm}0.9$ sec) and control groups($4.6{\pm}1.8$ sec). However the effect was significantly greater in the androgenized group. 3) Nociceptive sensitivity on 86th experimental day before administration of testosterone was significantly lower in the androgenized group($4.8{\pm}1.9$ sec) as compared to the control group($3.9{\pm}1.2$ sec). 4) Testosterone treatment on the 86th experimental day significantly lowered the nociceptive sensitivity in both groups, but the androgenized group($5.9{\pm}0.9$ sec) showed significantly lower post-treatment nociceptive sensitivity as compared to the control group($4.9{\pm}1.5$ sec). 5) Nociceptive sensitivity was decreased significantly after injection of testosterone once a day for two consecutive days in the androgenized group(${\Delta}2.1{\pm}1.0$ sec), but not in the control group(${\Delta}0.5{\pm}1.3$ sec). Conclusions : There may be a testosterone-related pain inhibitory system, the development of which is enhanced by exposure to testosterone in the neonatal period, and the activity of which is also mediated by testosterone in the later life.

• Physical Therapy Korea
• /
• v.5 no.2
• /
• pp.106-117
• /
• 1998

The pain is common among individuals with physical disabilities. It can interfere with therapy since patients with pain can become uncooperative and reluctant to move. This paper reviews the natural physiological mechanisms that can reduce pain perception, and considers physiological mechanisms which contribute to clinical pain by describing how the pain system changes its sensitivity depending upon the body's needs. The peripheral and central mechanisms contributing to sensitised nociceptive system are described with reference to the symptoms of clinical pain such as hyperalgesia, allodynia sopntaneous 'on-going'-projected and referred pain. It is suggested that in some chronic pain the nociceptive system maintains a state of sensitivity despite the absence of on-going tissue damage and under such circumstances the nociceptive system itself may have become dysfunctional. Such situations are often initiated by damage to nervous tissue which results in changes in the activity and organization of neuronal circuits within the central nervous system. The ability of the nociceptive system to operate in a suppressed state is also discussed with reference to pain modulation. The physical therapist can help facilitate the activation of these mechanisms through a combination of noninvasive modalities, functional activities, and the therapeutic use of self.

• Biomolecules & Therapeutics
• /
• v.27 no.2
• /
• pp.168-177
• /
• 2019

Dysregulation of excitatory neurotransmission has been implicated in the pathogenesis of neuropsychiatric disorders. Pharmacological inhibition of N-methyl-D-aspartate (NMDA) receptors is widely used to model neurobehavioral pathologies and underlying mechanisms. There is ample evidence that overstimulation of NMDA-dependent neurotransmission may induce neurobehavioral abnormalities, such as repetitive behaviors and hypersensitization to nociception and cognitive disruption, pharmacological modeling using NMDA has been limited due to the induction of neurotoxicity and blood brain barrier breakdown, especially in young animals. In this study, we examined the effects of intraperitoneal NMDA-administration on nociceptive and repetitive behaviors in ICR mice. Intraperitoneal injection of NMDA induced repetitive grooming and tail biting/licking behaviors in a dose- and age-dependent manner. Nociceptive and repetitive behaviors were more prominent in juvenile mice than adult mice. We did not observe extensive blood brain barrier breakdown or neuronal cell death after peritoneal injection of NMDA, indicating limited neurotoxic effects despite a significant increase in NMDA concentration in the cerebrospinal fluid. These findings suggest that the observed behavioral changes were not mediated by general NMDA toxicity. In the hot plate test, we found that the latency of paw licking and jumping decreased in the NMDA-exposed mice especially in the 75 mg/kg group, suggesting increased nociceptive sensitivity in NMDA-treated animals. Repetitive behaviors and increased pain sensitivity are often comorbid in psychiatric disorders (e.g., autism spectrum disorder). Therefore, the behavioral characteristics of intraperitoneal NMDA-administered mice described herein may be valuable for studying the mechanisms underlying relevant disorders and screening candidate therapeutic molecules.

• The Korean Journal of Pain
• /
• v.30 no.3
• /
• pp.197-206
• /
• 2017

Background: Pain with neuropathic characteristics is generally more severe and associated with a lower quality of life compared to nociceptive pain (NcP). Short form of the Douleur Neuropathique en 4 Questions (S-DN4) is one of the most used and reliable screening questionnaires and is reported to have good diagnostic properties. This study was aimed to cross-culturally validate the Hindi version of the S-DN4 in patients with various chronic pain conditions. Methods: The S-DN4 is already translated into the Hindi language by Mapi Research Trust. This study assessed the psychometric properties of the Hindi version of the S-DN4 including internal consistency and test-retest reliability after 3 days' post-baseline assessment. Diagnostic performance was also assessed. Results: One hundred sixty patients with chronic pain, 80 each in the neuropathic pain (NeP) present and NeP absent groups, were recruited. Patients with NeP present reported significantly higher S-DN4 scores in comparison to patients in the NeP absent group (mean (SD), 4.7 (1.7) vs. 1.8 (1.6), P < 0.01). The S-DN4 was found to have an AUC of 0.88 with adequate internal consistency (Cronbach's ${\alpha}=0.80$) and a test-retest reliability (ICC = 0.92) with an optimal cut-off value of 3 (Youden's index = 0.66, sensitivity and specificity of 88.7% and 77.5%). The diagnostic concordance rate between clinician diagnosis and the S-DN4 questionnaire was 83.1% (kappa = 0.66). Conclusions: Overall, the Hindi version of the S-DN4 has good internal consistency and test-retest reliability along with good diagnostic accuracy.

• International Journal of Oral Biology
• /
• v.34 no.3
• /
• pp.157-164
• /
• 2009

We recently described a novel animal model of trigeminal neuropathic pain following compression of the trigeminal ganglion (Ahn et al., 2009). In our present study, we adapted this model using male Sprague-Dawley rats weighing between 250-260 g and then analyzed the behavioral responses of these animals following modified chronic compression of the trigeminal ganglion. Under anesthesia, the rats were mounted onto a stereotaxic frame and a 4% agar solution ($10{\mu}L$) was injected in each case on the dorsal surface of the trigeminal ganglion to achieve compression without causing injury. In the control group, the rats received a sham operation without agar injection. Air-puff, acetone, and heat tests were performed at 3 days before and at 3, 7, 10, 14, 17, 21, 24, 30, 40, 55, and 70 days after surgery. Compression of the trigeminal ganglion produced nociceptive behavior in the trigeminal territory. Mechanical allodynia was established within 3 days and recovered to preoperative levels at approximately 60 days following compression. Mechanical hyperalgesia was also observed at 7 days after compression and persisted until the postoperative day 40. Cold hypersensitivity was established within 3 days after compression and lasted beyond postoperative day 55. In contrast, compression of the trigeminal ganglion did not produce any significant thermal hypersensitivity when compared with the sham operated group. These findings suggest that compression of the trigeminal ganglion without any injury produces prolonged nociceptive behavior and that our rat model is a useful system for further analysis of trigeminal neuralgia.

• Biomolecules & Therapeutics
• /
• v.3 no.4
• /
• pp.256-259
• /
• 1995

Antinociceptive and desensitizing effects of systemically administered capsaicinoids (capsaicin and KR25018) were investigated in guinea pig. Nociceptive sensitivity to chemical stimulus was examined to test sensory function, and the content of substance P-like immunorractivity (SP-LI) in bronchi was determined as a peripheral marker of capsaicin-sensitive primary afferent neurons. Guinea pigs were pretreated s.c. with several doses of capsaicin (1,2.5,5, 10 mg/kg) or KR25018 (1, 2.5, 5, 10 mg/kg) one week prior to the experiments. Frequency of eye wiping was significantly decreased by capsaicin and KR25018 in a pretreatment dosedependent manner. In capsaicin- or KR25018-pretreated guinea pigs, there was a significant loss of SP-LI in bronchial tissue extracts. In summary, a newly synthesized capsaicin analogue H725018 exhibited antinociceptive effect against chemical stimulus in guinea pig, with comparable potency to capsaicin. This desensitizing activity of capsaicin or KR25018 might be related to the loss of SP-LI in peripheral afferent nerves.

• Biomolecules & Therapeutics
• /
• v.31 no.4
• /
• pp.411-416
• /
• 2023

Methamphetamine (METH) is a powerful neurotoxic psychostimulant affecting dopamine transporter (DAT) activity and leading to continuous excess extracellular dopamine levels. Despite recent advances in the knowledge on neurobiological mechanisms underlying METH abuse, there are few effective pharmacotherapies to prevent METH abuse leading to brain damage and neuropsychiatric deficits. α-Pinene (APN) is one of the major monoterpenes derived from pine essential oils and has diverse biological properties including anti-nociceptive, anti-anxiolytic, antioxidant, and anti-inflammatory actions. In the present study, we investigated the therapeutic potential of APN in a METH abuse mice model. METH (1 mg/kg/day, i.p.) was injected into C57BL/6 mice for four alternative days, and a conditioned place preference (CPP) test was performed. The METH-administered group exhibited increased sensitivity to place preference and significantly decreased levels of dopamine-related markers such as dopamine 2 receptor (D2R) and tyrosine hydroxylase in the striatum of the mice. Moreover, METH caused apoptotic cell death by induction of inflammation and oxidative stress. Conversely, APN treatment (3 and 10 mg/kg, i.p.) significantly reduced METH-mediated place preference and restored the levels of D2R and tyrosine hydroxylase in the striatum. APN increased the anti-apoptotic Bcl-2 to pro-apoptotic Bax ratio and decreased the expression of inflammatory protein Iba-1. METH-induced lipid peroxidation was effectively mitigated by APN by up-regulation of antioxidant enzymes such as manganese-superoxide dismutase and glutamylcysteine synthase via activation of nuclear factor-erythroid 2-related factor 2. These results suggest that APN may have protective potential and be considered as a promising therapeutic agent for METH-induced drug addiction and neuronal damage.