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 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

Effect of Sympathetic Nerve Block on Acute Inflammatory Pain and Hyperalgesia

1997 ◽  
Vol 86 (2) ◽  
pp. 293-301 ◽  
Author(s):  
Juri L. Pedersen ◽  
George W. Rung ◽  
Henrik Kehlet
Keyword(s):  
Nerve Block ◽  
Acute Pain ◽  
Sympathetic Nerve ◽  
Inflammatory Pain ◽  
Secondary Hyperalgesia ◽  
Sympathetic Block ◽  
Nerve Blocks ◽  
Pain Thresholds ◽  
Heat Injury ◽  
Medial Surfaces

Background Sympathetic nerve blocks relieve pain in certain chronic pain states, but the role of the sympathetic pathways in acute pain is unclear. Thus the authors wanted to determine whether a sympathetic block could reduce acute pain and hyperalgesia after a heat injury in healthy volunteers. Methods The study was made as a randomized, single blinded investigation, in which the volunteers served as their own controls. A lumbar sympathetic nerve block and a contralateral placebo block were performed in 24 persons by injecting 10 ml bupivacaine (0.5%) and 10 ml saline, respectively. The duration and quality of blocks were evaluated by the sympatogalvanic skin response and skin temperature. Bilateral heat injuries were produced on the medial surfaces of the calves with a 50 x 25 mm thermode (47 degrees C, 7 min) 45 min after the blocks. Pain intensity induced by heat, pain thresholds to thermal and mechanical stimulation, and secondary hyperalgesia were assessed before block, after block, and 1, 2, 4, and 6 h after the heat injuries. Results Of the 24 volunteers, eight were excluded because of somatic block or incomplete sympathetic block. The study revealed no significant differences between sympathetic block and placebo for pain or mechanical allodynia during injury, or pain thresholds, pain responses to heat, or areas of secondary hyperalgesia after the injury. The comparisons were done for the period when the block was effective. Conclusion Sympathetic nerve block did not change acute inflammatory pain or hyperalgesia after a heat injury in human skin.

A multiple-dose double-blind randomized study to evaluate the safety, pharmacokinetics, pharmacodynamics and analgesic efficacy of the TRPV1 antagonist JNJ-39439335 (mavatrep)

2018 ◽  
Vol 18 (2) ◽  
pp. 151-164 ◽  
Author(s):  
Prasarn Manitpisitkul ◽  
Christopher M. Flores ◽  
John A. Moyer ◽  
Gary Romano ◽  
Kevin Shalayda ◽  
...  
Keyword(s):  
Adverse Events ◽  
Knee Osteoarthritis ◽  
Multiple Dose ◽  
Plasma Concentrations ◽  
Systemic Exposure ◽  
Analgesic Efficacy ◽  
Heat Pain ◽  
Double Blind ◽  
Cold Pain ◽  
Thermal Burns

Abstract Background and aims: This double-blind (DB), randomized, placebo-controlled, sequential-group, multiple-ascending dose, phase 1 study evaluated safety, pharmacokinetics and pharmacodynamics of JNJ-39439335 in healthy men (part 1), and in participants with knee osteoarthritis (part 2). Methods: Both parts 1 and 2 consisted of screening (upto 21 days), 21-day DB treatment phase [eight participants/group: JNJ-39439335 (part 1: 2–50 mg; part 2: 10–50 mg): n=6; placebo: n=2] and follow-up (total study duration ~10 weeks). Results: Plasma concentrations and systemic exposure of JNJ-39439335 increased in slightly higher than dose-proportional fashion (steady-state reached by day 14). Renal excretion of JNJ-39439335 was negligible. Marked dose-related increases in pharmacodynamic heat pain assessments were observed in JNJ-39439335-treated participants, which persisted throughout the treatment with no signs of tolerance with repeated dosing. No effect on pharmacodynamic cold pain or mechanical pain assessments were seen. Effects on pharmacodynamic capsaicin-induced flare assessments in JNJ-39439335-treated participants versus placebo were consistent with effects observed with single-dose, and did not demonstrate tolerance with multiple dosing. In participants with knee osteoarthritis, significant improvements versus placebo were observed in a stair-climbing-induced pain model. All JNJ-39439335-treated participants reported ≥1 treatment-emergent adverse events (TEAE); most common (≥50% incidence) TEAEs in part 1 were feeling hot (79%), thermohypoesthesia (71%), paresthesia (58%) and feeling cold (50%), and in part 2, were minor thermal burns (50%). Conclusions: JNJ-39439335 (doses 2–50 mg) was well-tolerated, and associated with acceptable multiple-dose pharmacokinetic profile. JNJ-39439335 demonstrated sustained pharmacodynamic effects (heat pain perception, heat pain latency, capsaicin-induced flare), and an efficacy signal in participants with osteoarthritis pain. Implications: Given the efficacy signal observed and the unique safety profile, larger phase 2 studies are needed to better understand the potential of JNJ-39439335 in the treatment of chronic pain. Analgesic efficacy of lower doses administered over a longer period of time and improved patient counseling techniques to reduce the minor thermal burns can be explored to minimize the adverse events.

AMPA/Kainate Antagonist LY293558 Reduces Capsaicin-evoked Hyperalgesia but Not Pain in Normal Skin in Humans 

1998 ◽  
Vol 89 (5) ◽  
pp. 1060-1067 ◽  
Author(s):  
Christine N. Sang ◽  
Meredith P. Hostetter ◽  
Richard H. Gracely ◽  
Amy S. Chappell ◽  
Darryle D. Schoepp ◽  
...  
Keyword(s):  
Side Effects ◽  
Mechanical Allodynia ◽  
Animal Studies ◽  
Statistical Significance ◽  
Normal Skin ◽  
Experimental Pain ◽  
Intradermal Injection ◽  
Spinal Neuron ◽  
Spontaneous Pain ◽  
Pain Thresholds

Background Animal studies suggest that alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-kainate (AMPA-KA) receptors are involved in pain processing. The effects of the competitive AMPA-KA antagonist LY293558 in two types of experimental pain in human volunteers, brief pain sensations in normal skin, and mechanical allodynia-pinprick hyperalgesia were studied after the injection of intradermal capsaicin. Methods Brief intravenous infusions of the competitive AMPA-KA antagonist LY293558 were given to 25 healthy volunteers to examine acute toxicity and analgesic effects. Fifteen volunteers then entered a double-blinded, three-period crossover study. In a Phase II study, LY293558 infusions (100% maximally tolerated dose vs. 33% maximally tolerated dose vs. placebo) began 10 min after intradermal injection of 250 microg capsaicin in volar forearm. Spontaneous pain, areas of mechanical allodynia and pinprick hyperalgesia, and side effects were determined every 5 min for 60 min. Results The median maximally tolerated dose was 1.3 +/- 0.4 (range, 0.9-2.0) mg/kg. Tests of cognitive and neurological function were unchanged. Dose-limiting side effects were hazy vision in 95% of volunteers and sedation in 40%. There were no significant changes in electrical or warm-cool detection and pain thresholds or heat pain thresholds. LY293558 had little effect on brief pain sensations in normal skin. Both high and low doses of LY293558 significantly reduced pain intensity, pain unpleasantness, and the area in which light brush evoked pain after intradermal capsaicin. There was a trend toward a dose-response effect of LY293558 on the area in which pinprick evoked pain after intradermal capsaicin, which did not reach statistical significance. Conclusions The authors infer that AMPA-KA receptor blockade reduces the spinal neuron sensitization that mediates capsaicin-evoked pain and allodynia. The low incidence of side effects at effective doses of LY293558 suggests that this class of drugs may prove to be useful in clinical pain states.

Basal Heat Pain Thresholds Predict Opioid Analgesia in Patients with Postherpetic Neuralgia

2006 ◽  
Vol 104 (6) ◽  
pp. 1243-1248 ◽  
Author(s):  
Robert R. Edwards ◽  
Jennifer A. Haythornthwaite ◽  
Prabhav Tella ◽  
Mitchell B. Max ◽  
Srinivasa Raja
Keyword(s):  
Postherpetic Neuralgia ◽  
Animal Studies ◽  
Patient Characteristics ◽  
High Heat ◽  
Large Individual ◽  
Opioid Analgesia ◽  
Heat Pain ◽  
Pain Thresholds ◽  
Opioid Treatment ◽  
Treatment Responses

Background A variety of analgesics have been studied in the treatment of postherpetic neuralgia, with several medications demonstrating some degree of efficacy. However, existing trials have documented large individual differences in treatment responses, and it is important to identify patient characteristics that predict the analgesic effectiveness of particular interventions. Several animal studies have indicated that reduced basal nociceptive sensitivity, in the form of relatively high heat pain thresholds, is associated with greater opioid analgesia, but this finding has not been applied to human studies of opioid treatment for chronic pain. Methods Using data from a previously published crossover trial of opioids and tricyclics in postherpetic neuralgia, the authors evaluated baseline thermal pain thresholds, assessed at a body site contralateral to the affected area, as a predictor of treatment responses. Results During opioid treatment, a greater reduction in pain and higher ratings of pain relief were observed in patients with relatively higher heat pain thresholds at baseline. Baseline pain thresholds did not predict responses to tricyclics or placebo. Interestingly, other individual-difference variables such as age and baseline pain intensity also significantly predicted opioid responses (i.e., higher baseline pain and younger age were related to greater opioid-associated pain reduction, with nearly 20% of the variance in opioid analgesia explained by these two factors). Conclusions These findings, which will require replication, suggest that pretreatment assessment of heat pain sensitivity might prove useful in identifying those patients most likely to respond to opioids.

scholarly journals Sweet taste does not modulate pain perception in adult humans

2020 ◽  
Vol 5 ◽  
pp. 43
Author(s):  
Elizabeth R Mooney ◽  
Alexander J Davies ◽  
Anthony E Pickering
Keyword(s):  
Animal Studies ◽  
Pain Threshold ◽  
Pain Perception ◽  
Specific Effect ◽  
Sweet Taste ◽  
Pain Tolerance ◽  
Heat Pain ◽  
Pain Thresholds ◽  
Heat Pain Threshold ◽  
Adult Humans

Background: Sugar is routinely used to comfort neonates undergoing painful procedures, and animal studies have shown that sucrose increases the time to withdrawal from painful stimuli. However, there are no published studies examining the effects of sweet substances on heat pain thresholds and percept in adult humans. Methods: Healthy adult volunteers (n=27, aged 18-48 years) were recruited to a controlled, double-blind, randomised, cross-over study to characterise the effect of tasting solutions of equivalent sweetness (10% sucrose and 0.016% sucralose) on warm detection and heat pain thresholds and the percept ratings of painfully hot stimuli. The effect of anticipation of a sweet taste on heat pain threshold was also assessed. Results: Tasting either sucrose or sucralose had no significant effect on the percept of an individually titrated hot stimulus (54.5±4.2 and 54.9±3.2 vs 53.2±3.5 for water, 0-100 visual analogue scale), on the warm detection or heat pain threshold (43.3±0.8, 43.2±0.8 vs 43.0±0.8°C). Anticipation of a sweet substance similarly did not affect heat pain thresholds. Conclusions: Sucrose and sucralose solutions had no analgesic effect when assessed using heat detection thresholds and percept ratings of painfully hot stimuli despite being perceived as sweeter and more pleasant than water. These findings are in contrast to results reported from previous animal studies in which thermal analgesia from sweet solutions is robust. Given the ubiquitous availability of sugar rich drinks in the modern environment, the lack of observable effect may be due to an insufficient hedonic value of the test solutions when compared to the experience of a laboratory rodent. Alternatively, sweet tastes may have a specific effect on pain tolerance rather than the threshold and acute percept measures assayed in this study.

scholarly journals Sweet taste does not modulate pain perception in adult humans

2020 ◽  
Vol 5 ◽  
pp. 43 ◽  
Author(s):  
Elizabeth R Mooney ◽  
Alexander J Davies ◽  
Anthony E Pickering
Keyword(s):  
Animal Studies ◽  
Pain Threshold ◽  
Pain Perception ◽  
Specific Effect ◽  
Sweet Taste ◽  
Pain Tolerance ◽  
Heat Pain ◽  
Pain Thresholds ◽  
Heat Pain Threshold ◽  
Adult Humans

Background: It is commonly observed that humans who are in pain or discomfort seek solace in the form of sweet foods and drinks. Sugar is routinely used to comfort neonates undergoing painful procedures, and animal studies have shown that sucrose increases the time to withdrawal from painful stimuli. However, there are no published studies examining the effects of sweet substances on heat pain thresholds and percept in adult humans. Methods: Healthy adult volunteers (n=27, aged 18-48 years) were recruited to a controlled, double-blind, randomised, cross-over study to characterise the effect of tasting solutions of equivalent sweetness (10% sucrose and 0.016% sucralose) on warm detection and heat pain thresholds and the percept ratings of painfully hot stimuli. The effect of anticipation of a sweet taste on heat pain threshold was also assessed. Results: Tasting either sucrose or sucralose had no significant effect on the percept of an individually titrated hot stimulus (54.5±4.2 and 54.9±3.2 vs 53.2±3.5 for water, 0-100 visual analogue scale), on the warm detection or heat pain threshold (43.3±0.8, 43.2±0.8 vs 43.0±0.8°C). Anticipation of a sweet substance similarly did not affect heat pain thresholds. Conclusions: Sucrose and sucralose solutions had no analgesic effect when assessed using heat detection thresholds and percept ratings of painfully hot stimuli despite being perceived as sweeter and more pleasant than water. These findings are in contrast to results reported from previous animal studies in which thermal analgesia from sweet solutions is robust. Given the ubiquitous availability of sugar rich drinks in the modern environment, the lack of observable effect may be due to an insufficient hedonic value of the test solutions when compared to the experience of a laboratory rodent. Alternatively, sweet tastes may have a specific effect on pain tolerance rather than the threshold and acute percept measures assayed in this study.

scholarly journals Evaluation on immediate analgesic efficacy and safety of Kai-Hou-Jian spray (children’s type) in treating sore throat caused by acute pharyngitis and tonsillitis in children: study protocol for a randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yan-ning Ma ◽  
Cheng-liang Zhong ◽  
Si-yuan Hu ◽  
Qiu-han Cai ◽  
Sheng-xuan Guo
Keyword(s):  
Clinical Trial ◽  
Sore Throat ◽  
Controlled Trial ◽  
Analgesic Efficacy ◽  
Effective Rate ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Acute Pharyngitis ◽  
Randomized Controlled ◽  
Parallel Group

Abstract Background Acute pharyngitis and tonsillitis are common respiratory diseases for which children seek medical care. Their main clinical manifestation is sore throat which interferes with patients’ quality of life. However, there is no proven effective or safe method to treat it. It is necessary to find an excellent strategy to reduce sore throat and reduce the burden of acute illness. We designed the randomized controlled trial with the characteristics of traditional Chinese medicine (TCM) to determine the clinical positioning of Kai-Hou-Jian spray (children’s type) (KHJS) through evidence-based research. This trial aims to evaluate the immediate analgesic efficacy of KHJS on sore throat caused by acute pharyngitis and tonsillitis (wind-heat syndrome/heat exuberance in lung and stomach syndrome) in children and to observe its safety. Methods/design This is a prospective, multicenter, randomized, double-blind, parallel-group, placebo-controlled trial. It will include 240 children with acute pharyngitis/tonsillitis from 7 study sites across China. All participants are randomly assigned to two parallel treatment groups, one with KHJS and the other with placebo sprays, for 5 consecutive days. The primary outcome is the time of analgesic onset. Secondary outcomes include duration of analgesic effect, area under time curve of 0–3 h Wong-Baker FACES Pain Rating Scale (WBS) score (AUC0-3 h), rate of analgesic onset, rate of disappearance of sore throat, changes of WBS score (in days), effective rate of pharyngeal signs, and effective rate of TCM syndrome. The incidence of adverse events during the trial is the primary safety outcome. In addition, vital signs and laboratory tests before and after medication are monitored. Discussion To our knowledge, this will be the first clinical trial to explore the immediate analgesic efficacy of a Chinese patent medicine spray for acute pharyngitis/tonsillitis induced sore throat in children in a multicenter, randomized, double-blinded, parallel-group, placebo-controlled manner. Not only might it prove the efficacy and safety of KHJS in the treatment of sore throat caused by acute pharyngitis/tonsillitis in children, but it might also provide evidence for the treatment of acute sore throat with Chinese herbal medicine. Trial registration A multicenter, randomized, double-blind, very low-dose, parallel controlled trial for the immediate analgesic effect and safety of Kai-Hou- Jian spray (children's type) in the treatment of sore throat caused by acute pharyngitis and tonsillitis in children. Chinese Clinical Trial Registry ChiCTR2000031599. Registered on 5 April 2020

scholarly journals GABA Supplementation Negatively Affects Cognitive Flexibility Independent of Tyrosine

2021 ◽  
Vol 10 (9) ◽  
pp. 1807
Author(s):  
Lee Wei Lim ◽  
Luca Aquili
Keyword(s):  
Cognitive Flexibility ◽  
Task Switching ◽  
Animal Studies ◽  
Preliminary Evidence ◽  
Interactive Effects ◽  
Dopamine Synthesis ◽  
Double Blind ◽  
Performance Improvements ◽  
Two Measures ◽  
Healthy Participants

Increasing evidence, particularly from animal studies, suggests that dopamine and GABA are important modulators of cognitive flexibility. In humans, increasing dopamine synthesis through its precursor tyrosine has been shown to result in performance improvements, but few studies have reported the effects of GABA supplementation in healthy participants. We conducted a double-blind, placebo-controlled, randomized experiment to test the interactive effects of tyrosine and GABA administration on two measures of cognitive flexibility, response inhibition and task switching. A total of 48 healthy volunteers were split into four groups (placebo, tyrosine alone, GABA alone, and tyrosine and GABA combined). They completed cognitive flexibility tasks at baseline and after drug administration. We found that tyrosine alone had no impact on the measures of cognitive flexibility, whereas GABA alone and in combination with tyrosine worsened task switching. Our results provide preliminary evidence that putative increases in GABA and dopamine synthesis do not interact to affect cognitive flexibility performance.

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