scholarly journals The Analgesic Effects of Celecoxib on the Formalin-induced Short- and Long-term Inflammatory Pain

2017 ◽  
Vol 4 (20;4) ◽  
pp. E575-584 ◽  
Author(s):  
Ya-Qun Zhao
Keyword(s):  
Inflammatory Pain ◽  
Formalin Test ◽  
Formalin Injection ◽  
Spontaneous Pain ◽  
Second Phase ◽  
Secondary Hyperalgesia ◽  
Analgesic Effects ◽  
Gastrointestinal Side Effects ◽  
Short And Long Term

The non-steroidal anti-inflammatory drug celecoxib has long been used for reducing pain, in spite of moderate gastrointestinal side effects. In previous studies, it has been shown that celecoxib can inhibit formalin-induced spontaneous pain and secondary hyperalgesia. Injecting formalin into a rodent’s hind paw not only induces acute pain behaviors, but also produces long-lasting hyperalgesia. Whether celecoxib can also have long-lasting effects is still unknown. Our results show that pretreatment with an intraperitoneal injection of celecoxib at one hour before formalin injection induced inhibition on the spontaneous flinch and licking behaviors in the second phase but not the first phase. Meanwhile, FOS expressions were also reduced with celecoxib pretreatment. Consecutive administration of celecoxib also protects the hind paw from hypoalgesia and relieves formalininduced, long-lasting hyperalgesia in the ipsilateral hind paw. These analgesic effects may be related to suppression of the activation of neurons and astrocytes indicated by FOS and GFAP expressions. Based on the above findings, celecoxib demonstrated analgesic effects not only on acute spontaneous pain behavior but also on long-lasting hyperalgesia induced by formalin injection. The inhibition of neurons and astrocytes by celecoxib may be possible reasons for its analgesia. Key words: Formalin test, celecoxib, FOS, GFAP, hyperalgesia

scholarly journals Analgesic characteristics of a newly developed α2δ ligand, mirogabalin, on inflammatory pain

2021 ◽  
Vol 17 ◽  
pp. 174480692110521
Author(s):  
Shuji Komatsu ◽  
Shingo Nakamura ◽  
Takahiro Nonaka ◽  
Toshihiko Yamada ◽  
Tatsuo Yamamoto
Keyword(s):  
Oral Administration ◽  
Inflammatory Pain ◽  
Analgesic Effect ◽  
Time Course ◽  
Formalin Test ◽  
Formalin Injection ◽  
Intracerebroventricular Administration ◽  
Analgesic Effects ◽  
Adrenergic Antagonist ◽  
Sites Of Action

Mirogabalin is a novel α2δ ligand approved in Japan for the treatment of peripheral neuropathic pain. However, the sites of action of α2δ ligands to produce analgesic effects on inflammatory pain remain unclear. In this study, we investigated the analgesic effect and site of action of mirogabalin using the rat formalin test, an acute inflammatory pain model. Mirogabalin was administered orally, intrathecally, and intracerebroventricularly. Open field tests were performed to evaluate the effect of oral-, intrathecally, and intracerebroventricularly administered mirogabalin on locomotor activity and orientation ability. Oral mirogabalin produced an analgesic effect when the formalin test was performed 4 h, but not 1 or 2 h, after oral administration. Intrathecal, but not intracerebroventricular, administration of mirogabalin produced analgesic effects when mirogabalin was administered 10 min before formalin injection. These analgesic effects were not antagonized by idazoxan, an α2 adrenergic antagonist; WAY100135, a 5-HT1A antagonist; or naloxone, an opioid receptor antagonist. Mirogabalin attenuated moving distances 1 and 2 h after oral administration and 10 min after intracerebroventricular administration, but not 10 min after intrathecal administration. In the oral administration group, the time course of the analgesic effect was different from that of moving distance. In the intracerebroventricular group, mirogabalin attenuated moving distances but did not produce an analgesic effect. In the intrathecal group, mirogabalin produced an analgesic effect but did not affect moving distances. These findings suggest that the analgesic effect of mirogabalin on the rat formalin test is mediated by spinal action and not by the activation of α2, 5-HT1A, or opioid receptors, and that the inhibitory effect of mirogabalin on moving distances is mediated by the supraspinal brain.

Can the use of physical modalities for pain control be rationalized by the research evidence?

1991 ◽  
Vol 69 (5) ◽  
pp. 704-712 ◽  
Author(s):  
C. Elaine Chapman
Keyword(s):  
Musculoskeletal Pain ◽  
Pain Control ◽  
Research Evidence ◽  
Power Laser ◽  
Short Term ◽  
Analgesic Effects ◽  
Short And Long Term ◽  
Continued Use ◽  
Physical Modalities

Physical modalities, including cold and heat, are widely used in the conservative management of pain associated with musculoskeletal disorders. This review has critically appraised the literature supporting the use of these modalities in the treatment of musculoskeletal pain. It was concluded that, apart from a few exceptions and in a few types of disorders, existing evidence does not support the use of these modalities in long-term pain control. There was, however, evidence that several modalities, specifically cold and a form of deep heat (shortwave diathermy), do have short-lived analgesic effects and so may contribute to more painfree function in the short term. Further research is clearly warranted to define the short- and long-term therapeutic efficacy of physical modalities in the treatment of musculoskeletal pain to justify their continued use in clinical practice.Key words: pain control, cold, heat, ultrasound, low-power laser.

scholarly journals Lack of Analgesia by Oral Standardized Cannabis Extract on Acute Inflammatory Pain and Hyperalgesia in Volunteers

2008 ◽  
Vol 109 (1) ◽  
pp. 101-110 ◽  
Author(s):  
Birgit Kraft ◽  
Nathalie A. Frickey ◽  
Rainer M. Kaufmann ◽  
Marcus Reif ◽  
Richard Frey ◽  
...  
Keyword(s):  
Inflammatory Pain ◽  
Animal Studies ◽  
Analgesic Efficacy ◽  
Spontaneous Pain ◽  
Heat Pain ◽  
Secondary Hyperalgesia ◽  
Double Blind ◽  
Pain Thresholds ◽  
Healthy Female ◽  
Cannabis Extract

Background Cannabinoid-induced analgesia was shown in animal studies of acute inflammatory and neuropathic pain. In humans, controlled clinical trials with Delta-tetrahydrocannabinol or other cannabinoids demonstrated analgesic efficacy in chronic pain syndromes, whereas the data in acute pain were less conclusive. Therefore, the aim of this study was to investigate the effects of oral cannabis extract in two different human models of acute inflammatory pain and hyperalgesia. Methods The authors conducted a double-blind, crossover study in 18 healthy female volunteers. Capsules containing Delta-tetrahydrocannabinol-standardized cannabis extract or active placebo were orally administered. A circular sunburn spot was induced at one upper leg. Heat and electrical pain thresholds were determined at the erythema, the area of secondary hyperalgesia, and the contralateral leg. Intradermal capsaicin-evoked pain and areas of flare and secondary hyperalgesia were measured. Primary outcome parameters were heat pain thresholds in the sunburn erythema and the capsaicin-evoked area of secondary hyperalgesia. Secondary measures were electrical pain thresholds, sunburn-induced secondary hyperalgesia, and capsaicin-induced pain. Results Cannabis extract did not affect heat pain thresholds in the sunburn model. Electrical thresholds (250 Hz) were significantly lower compared with baseline and placebo. In the capsaicin model, the area of secondary hyperalgesia, flare, and spontaneous pain were not altered. Conclusion To conclude, no analgesic or antihyperalgesic activity of cannabis extract was found in the experiments. Moreover, the results even point to the development of a hyperalgesic state under cannabinoids. Together with previous data, the current results suggest that cannabinoids are not effective analgesics for the treatment of acute nociceptive pain in humans.

scholarly journals Vitamin B12 and ketorolac on pain in Long Evans rats

2016 ◽  
Vol 11 (2) ◽  
pp. 63-69
Author(s):  
Md Mizanur Rahman ◽  
Noorzahan Begum ◽  
Taskina Ali ◽  
Mahadi Abdur Rouf ◽  
Shahriar Masood
Keyword(s):  
Vitamin B12 ◽  
Inflammatory Pain ◽  
Formalin Test ◽  
Late Phase ◽  
Total Duration ◽  
Analgesic Effects ◽  
Long Evans ◽  
The Right ◽  
Post Hoc ◽  
Medical University

Background: Effects of vitamin B12 on pain have been demonstrated in different animal and human studies. But comparison of these effects with similar effects of ketorolac tromethamine (KT) and their combination have not been established.Objective: To assess the effects of vitamin B12 on pain and also to compare them with those of the combinations of vitamin B12 with KT in rat models.Methods: This experimental study was conducted in the Department of Physiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, from March 2015 to February 2016. For this, 20 (twenty) Long Evans rats (215±35 gm) of both sexes were divided into control (A, with 5 ml/kg normal saline) and experimental (B1, with 15 mg/kg B12; B2, with 10 mg/kg KT; B3, with B12+KT) groups with 5 rats in each group. All the drugs and vitamin were administered intraperitoneally in a single dose just one hour before formalin test. To evaluate the treatments’ effect on nociceptive pain, early phase (1st- 5th minutes); on central analgesic system, interphase (6th-15th minutes); and on inflammatory pain, late phase (16th-60th minutes) of the formalin test, were observed. In all phases, total frequency of jerking and total duration of flexing and licking of the right hind paw were counted after administration of subcutaneous formalin (50 ?l, 2.5%) injection. Statistical analysis was done by ANOVA, followed by Bonferroni post hoc test. In the interpretation of results, p?0.05 was considered as significant.Results: B12 lowered only the jerking frequency and KT lowered both jerking frequency and flexinglicking duration significantly (p?0.001) in the late phase of formalin test. On the other hand, combination of B12 and KT significantly (p?0.001) lowered both the study variables in all 3 phases of formalin test.Conclusion: From this study it may be concluded that, vitamin B12 possess analgesic effects and combination of B12 with KT is more effective than those of their individual administration.Bangladesh Soc Physiol. 2016, December; 11(2): 63-69

scholarly journals The analgesic effect of refeeding on acute and chronic inflammatory pain

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jeong-Yun Lee ◽  
Grace J. Lee ◽  
Pa Reum Lee ◽  
Chan Hee Won ◽  
Doyun Kim ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Inflammatory Pain ◽  
Analgesic Effect ◽  
Cannabinoid Receptor ◽  
Pain Behavior ◽  
Spontaneous Pain ◽  
Second Phase ◽  
Pain Model ◽  
Chronic Inflammatory Pain ◽  
Effect Of Food

AbstractPain is susceptible to various cognitive factors. Suppression of pain by hunger is well known, but the effect of food intake after fasting (i.e. refeeding) on pain remains unknown. In the present study, we examined whether inflammatory pain behavior is affected by 24 h fasting and 2 h refeeding. In formalin-induced acute inflammatory pain model, fasting suppressed pain behavior only in the second phase and the analgesic effect was also observed after refeeding. Furthermore, in Complete Freund’s adjuvant-induced chronic inflammatory pain model, both fasting and refeeding reduced spontaneous pain response. Refeeding with non-calorie agar produced an analgesic effect. Besides, intraperitoneal (i.p.) administration of glucose after fasting, which mimics calorie recovery following refeeding, induced analgesic effect. Administration of opioid receptor antagonist (naloxone, i.p.) and cannabinoid receptor antagonist (SR 141716, i.p.) reversed fasting-induced analgesia, but did not affect refeeding-induced analgesia in acute inflammatory pain model. Taken together, our results show that refeeding produce analgesia in inflammatory pain condition, which is associated with eating behavior and calorie recovery effect.

scholarly journals The Effects of Exposure to Repeated Minor Pain During the Neonatal Period on Formalin Pain Behavior and Thermal Withdrawal Latencies

2003 ◽  
Vol 8 (4) ◽  
pp. 213-217 ◽  
Author(s):  
C Celeste Johnston ◽  
Claire-Dominique Walker
Keyword(s):  
Formalin Test ◽  
Thermal Stimulation ◽  
Neonatal Rat ◽  
Maternal Behaviour ◽  
Long Term Effects ◽  
Thermal Thresholds ◽  
Rat Pups ◽  
Short And Long Term ◽  
Repeated Pain

Preterm infants undergoing untreated, repeated painful procedures as part of their early experience are more likely to behave differently to pain as they mature than infants who were born at term and did not experience excessive exogenous pain. The neonatal rat model was used to investigate the short- and long-term effects of repeated pain in infancy on later development of pain responses. Newborn rat pups were randomly assigned by litter to be left unhandled (UH), handled by being removed from the dam for 15 min four times daily (H), and being handled and receiving pain from a paw prick with a 26G needle four times daily (P)on postnatal days (PD) 2 through 8 (PD2-PD8). Maternal behaviour and grooming of pups on their return to the nest were recorded at PD6 for H and P pups. At PD15, PD36 and PD65, animals were first tested for latency to thermal stimulation threshold using the Hargreaves test and then for inflammatory pain using the formalin test. Pups in the HP group received significantly more grooming from their mothers (359 s) than pups in the H group (295 s, P<0.0001). When accounting for differences in maternal grooming, a decreased thermal threshold in the P group compared with the H group (6.04 s versus 5.3 s, P<0.05) was found, although the correlations were not significant between maternal grooming and thermal thresholds. No group differences were seen with the formalin test. Interestingly, age was a significant factor in both tests, with younger animals showing fewer pain behaviours regardless of group or maternal grooming of the pup. Sex was significant at one age only in latency to thermal stimulation testing. The results suggest that changes in maternal care may be an important factor mediating the long-term effects of repeated neonatal experiences of pain.

Preemptive Analgesic Effects of Steroid Anesthesia with Alphaxalone in the Rat Formalin Test

1996 ◽  
Vol 84 (3) ◽  
pp. 572-579 ◽  
Author(s):  
Ian Gilron ◽  
Terence J. Coderre
Keyword(s):  
Central Sensitization ◽  
Formalin Test ◽  
Formalin Injection ◽  
Receptor Subtypes ◽  
Gaba A ◽  
Analgesic Effects ◽  
Progesterone Metabolites ◽  
Behavior Of Rats

Background The role of preemptive treatment with volatile and intravenous anesthetics has been examined in previous studies using the rat formalin test. Evidence describing analgesic properties of the gamma-amino butyric acid-ergic (GABAergic) steroid anesthetics, such as alphaxalone, suggest that they may suppress the development of central sensitization to pain. This study examined the preemptive effects of phaxalone in comparison with other GABAergic anesthetics, propofol and pentobarbital. Methods The pain behavior of rats was evaluated (using the previously validated weighted scores method of behavioral rating) 15-60 min after subcutaneous hind paw injection of 50 microg 1.5% formalin. In each trial, anesthetics and their respective vehicles were administered by tail-vein injection either 0.5-10 min before or 5 min after, formalin injection. When analgesic effects were observed with any of these agents, further studies were conducted with a GABA(A) receptor antagonist in an attempt to confirm a specific receptor-mediated action of the agent. Results Alphaxalone pretreatment produced transient analgesia in the early part of phase 2, which was not observed in rats posttreated with alphaxalone. The analgesic effect of alphaxalone was antagonized by picrotoxin, as well. Neither pentobarbital nor propofol showed any analgesic effects at the doses used in our study. Conclusions Whereas alphaxalone was shown to produce preemptive analgesia through its action at the GABA(A) receptor, pentobarbital and propofol, which also are known to act at this site, showed no analgesic effects. The diversity of receptor subtypes and functional complexity of GABA(A) receptors is such that steroid anesthetics may have effects that are different from other GABAergic agents. Further research into the role of progesterone metabolites and steroid anesthetics in the prevention of central sensitization may have clinical implications for the treatment of acute or chronic pain.

Inhibition of Nociception-induced Spinal Sensitization by Anesthetic Agents 

1995 ◽  
Vol 82 (1) ◽  
pp. 259-266 ◽  
Author(s):  
Therese C. O'Connor ◽  
Stephen E. Abram
Keyword(s):  
Nitrous Oxide ◽  
Formalin Test ◽  
Phase 1 ◽  
Formalin Injection ◽  
Second Phase ◽  
Nociceptive Response ◽  
Phase 2 ◽  
Anesthetic Agents ◽  
C Fiber ◽  
Spinal Sensitization

Background Subcutaneous injection of dilute formalin in the hind paw of the rat produces a biphasic nociceptive response. Initial C-fiber activity is accompanied by flinching of the paw for about 5 min (phase 1), followed by cessation of activity and resumption of flinching beginning 15 min after injection and lasting about 40 min or more (phase 2). The second phase depends on changes in dorsal horn cell function that occur shortly after the initial C-fiber discharge. It was previously shown that isoflurane, administered during phase 1, reduced phase 2 activity, but a combination of isoflurane and nitrous oxide given throughout phase 1 did not suppress spinal sensitization. The same model was used to determine the effects of several inhalation and intravenous anesthetic agents on phase 2 of the formalin test. Methods The formalin test was carried out on male Sprague-Dawley rats. Animals anesthetized briefly with halothane to facilitate formalin injection, were compared to animals that received 1 MAC anesthesia from 5 min before to 6 min after formalin injection using halothane, enflurane, isoflurane, desflurane, or 70% N2O, or a combination of nitrous oxide plus 1 MAC halothane. Animals that were given intravenous saline immediately before injection of formalin were compared to animals given either 20 mg/kg intravenous thiopental just before formalin injection or 10 mg/kg intravenous propofol just before and 3 mg/kg immediately after formalin injection. Flinches/minute were counted at 1 and 5 min after formalin injection and thereafter at 5-min intervals for 1 h. The total of 1- and 5-min flinches were considered phase 1 activity and the total of 10-60-min flinches were considered phase 2. Total phase 2 activity was compared between groups using one-way analysis of variance. Results Animals that received halothane, enflurane, isoflurane, desflurane, or nitrous oxide during phase 1 demonstrated a significant decrease in phase 2 activity when compared to controls, while those that received a combination of nitrous oxide and halothane exhibited no difference. Animals that received intravenous thiopental anesthesia during phase 1 demonstrated no difference in phase 2 activity when compared to controls, whereas those that received propofol during phase 1 demonstrated a significant decrease of phase 2 activity. Conclusions Volatile anesthetics or nitrous oxide significantly suppress spinal sensitization, whereas the combination of nitrous oxide plus halothane causes no suppression. Thiopental does not affect spinal sensitization, whereas propofol causes significant suppression. These results may have important implications regarding the development of postoperative pain.

scholarly journals Electroacupuncture Stimulation Alleviates CFA-Induced Inflammatory Pain Via Suppressing P2X3 Expression

2019 ◽  
Vol 20 (13) ◽  
pp. 3248 ◽  
Author(s):  
Xuaner Xiang ◽  
Sisi Wang ◽  
Fangbing Shao ◽  
Junfan Fang ◽  
Yingling Xu ◽  
...  
Keyword(s):  
Inflammatory Pain ◽  
Analgesic Effect ◽  
Purinergic Receptor ◽  
Pathological Process ◽  
Spinal Cord Dorsal Horn ◽  
Chronic Inflammatory Pain ◽  
Withdrawal Threshold ◽  
Analgesic Effects ◽  
Spinal Cord Dorsal

Chronic inflammatory pain is one of the most common complaints that seriously affects patients’ quality of life. Previous studies have demonstrated that the analgesic effect of electroacupuncture (EA) stimulation on inflammatory pain is related to its frequency. In this study, we focused on whether the analgesic effects of EA are related to the period of stimulation. Purinergic receptor P2X3 (P2X3) is involved in the pathological process underlying chronic inflammatory pain and neuropathic pain. We hypothesized that 100 Hz EA stimulation alleviated Freund’s complete adjuvant (CFA) induced inflammatory pain via regulating P2X3 expression in the dorsal root ganglion (DRG) and/or spinal cord dorsal horn (SCDH). We also assumed that the analgesic effect of EA might be related to the period of stimulation. We found that both short-term (three day) and long-term (14 day) 100 Hz EA stimulation effectively increased the paw withdrawal threshold (PWT) and reversed the elevation of P2X3 in the DRG and SCDH of CFA rats. However, the analgesic effects of 100 Hz EA were not dependent on the period of stimulation. Moreover, P2X3 inhibition or activation may contribute to or attenuate the analgesic effects of 100 Hz EA on CFA-induced inflammatory pain. This result indicated that EA reduced pain hypersensitivity through P2X3 modulation.

Synergistic Antinociceptive Effect of Amitriptyline and Morphine in the Rat Orofacial Formalin Test

2004 ◽  
Vol 100 (3) ◽  
pp. 690-696 ◽  
Author(s):  
Philippe Luccarini ◽  
Laurent Perrier ◽  
Céline Dégoulange ◽  
Anne-Marie Gaydier ◽  
Radhouane Dallel
Keyword(s):  
Confidence Interval ◽  
Inflammatory Pain ◽  
Formalin Test ◽  
Antinociceptive Effect ◽  
Second Phase ◽  
Isobolographic Analysis ◽  
Antinociceptive Effects ◽  
Analgesic Agents ◽  
Rubbing Behavior ◽  
Orofacial Formalin Test

Background Combination therapy is often used to increase the clinical utility of analgesic agents. The coadministration of two compounds may achieve analgesia at doses lower than those required for either compound alone, leading to enhanced pain relief and reduction of adverse effects. Herein, the authors describe the effect of coadministration of morphine and amitriptyline on cutaneous orofacial inflammatory pain in rats. Methods Amitriptyline, morphine, or the combination of amitriptyline and morphine was administered systemically to rats, and antinociceptive effects were determined by means of the rat orofacial formalin test. Isobolographic analysis was used to define the nature of the interactions between morphine and amitriptyline. Results Amitriptyline as well as morphine produced a dose-related inhibition in the first phase and the second phase of rubbing activity. ED50 values against rubbing behavior were 14.6 mg/kg (95% confidence interval, 10.2-33.5 mg/kg) and 1.3 mg/kg (95% confidence interval, 1.0-1.7 mg/kg) for amitriptyline and morphine, respectively. Combinations of increasing fractional increments of amitriptyline and morphine ED50 doses produced a synergistic effect against rubbing behavior, as revealed by isobolographic analysis. Conclusions The current study suggests that systemic amitriptyline and morphine synergistically inhibit cutaneous orofacial inflammatory pain in rats.

Sign in / Sign up

Export Citation Format

Share Document