The Role of Organic Small Molecules in Pain Management

Cuesta, Sebastián; Meneses, Lorena

doi:10.3390/molecules26134029

Cited by 12 publications

(19 citation statements)

References 152 publications

(249 reference statements)

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“…It interferes with all personal, familial and social activities. Thus patients ask for drugs chosen among the many painkillers available [ 12 ]. With such treatment it is possible that the pain is reduced or cancelled; however, in some cases the therapy may not work and the patient returns to the physician, who will change the drug, increase the dose or add another drug.…”

Section: Discussionmentioning

confidence: 99%

Food-Specific IgG4 Antibody-Guided Exclusion Diet Improves Conditions of Patients with Chronic Pain

Casini

Fatighenti²,

Giannantoni³

et al. 2022

Pain Ther

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Introduction Chronic pain is related to gastrointestinal (GI) functions because food components affect inflammation and pain through their action on the GI immune and/or neural system and because many analgesics interact with the gut to alter its structure and function. Immunoglobulin G4 (IgG4) are food-specific antibodies resulting from exposure of the gut immune system to nutrients. High IgG4 levels have been found to be associated with inflammation. Methods IgG4 were determined (both with the rapid test and enzyme-linked immunosorbent assay, ELISA) in men and women outpatients with chronic pain. All subjects were asked to exclude for 4 weeks all foods to which they had high blood levels of IgG4 antibodies. Pain and quality of life questionnaires were administered before (visit 1) and after (visit 2) the personalized exclusion diet period. Visual analogue scale (VAS), Italian Pain Questionnaire (QUID) and Margolis (MA) questionnaires were administered to determine pain intensity, pain features and pain extent, while Short Form Health Survey (SF-36) and Profile of Mood States (POMS) were used to test the quality of life and mood state. The nutritional status was evaluated in all subjects. Subject groups were women of reproductive age (pre-MW), women in menopause for at least 1 year (MW) and men. Results Fifty-four subjects with chronic pain ( n = 12 neuropathic, n = 14 diffuse pain, n = 11 headache, n = 17 low back pain) completed the two visits and the 1-month exclusion diet. At visit 1, 47 (87%) subjects showed medium/high levels of IgG4 to at least one food. The foods showing the highest IgG4 values were eggs, dairy products, cereals and dried fruit. At visit 2, IgG4 levels were decreased, increased or unchanged. In all groups, the 4-week exclusion diet resulted in a significant reduction in all pain measures and an improvement of quality of life parameters. In particular, at visit 2, the VAS score determined in the morning decreased by more than 50%. Conclusions A food elimination diet based on IgG4 antibody levels may be effective in reducing pain and improving quality of life in patients with chronic pain. Supplementary Information The online version contains supplementary material available at 10.1007/s40122-022-00391-z.

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Section: Discussionmentioning

confidence: 99%

Food-Specific IgG4 Antibody-Guided Exclusion Diet Improves Conditions of Patients with Chronic Pain

Casini

Fatighenti²,

Giannantoni³

et al. 2022

Pain Ther

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“…Therefore, neuroinflammation and neuropathic pain can be partly reversed by inhibiting key proinflammatory cytokines and chemokines [ 20 ]. Nonsteroidal anti-inflammatory drugs (NSAIDs) are typically used for relieving inflammatory pain by inhibiting the enzyme cyclooxygenase (COX) and suppressing prostaglandin synthesis [ 21 ]. Moreover, NSAIDs have been widely used for the treatment of hyperalgesia, allodynia, and inflammation in both acute and chronic pain [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Synergistic Antinociceptive Effects of Indomethacin–Pregabalin and Meloxicam–Pregabalin in Paclitaxel-Induced Neuropathic Pain

Ma¹,

Liu²,

Liang³

et al. 2022

Biomedicines

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Neuropathic pain is often closely associated with nerve injury or inflammation, and the role of traditional nonsteroidal anti-inflammatory drugs as adjuvants for treating chemotherapy-induced peripheral neuropathic pain remains unclear. In this study, the potential synergistic antinociceptive effects of indomethacin–pregabalin and meloxicam–pregabalin were evaluated in paclitaxel-induced neuropathic pain and carrageenan-induced inflammatory pain in rodents. Although indomethacin and meloxicam alone only slightly relieved mechanical allodynia in the above two models, isobolographic analysis showed that the combination of indomethacin or meloxicam with pregabalin produced significant synergistic antinociceptive effects for paclitaxel-induced neuropathic pain (IN-PGB, experimental ED25 = [4.41 (3.13–5.82)] mg/kg, theoretical ED25 = [8.50 (6.62–10.32)] mg/kg; MEL-PGB, experimental ED25 = [3.96 (2.62–5.46)] mg/kg, theoretical ED25 = [7.52 (5.73–9.39)] mg/kg). In addition, MEL-PGB dosed via intraplantar injection into the left paw, intragastric injection, or intraperitoneal injection reversed paclitaxel-induced allodynia, indicating that they may act at multiple sites in the neuroaxis and periphery. However, indomethacin–pregabalin and meloxicam–pregabalin exerted antagonistic antiallodynic interactions in carrageenan-induced inflammatory pain in rats. Taken together, coadministration of indomethacin or meloxicam with pregabalin may possess potential therapeutic advantages for treating chemotherapy-induced neuropathic pain.

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“…Drug combinations are a therapeutic strategy for improving pharmacological efficacy. Concerning pain, different combinations have been developed for its treatment [ 1 , 2 ]. The study of synergism has resulted in the development of drug combinations to improve the analgesic efficacy and, at the same time, to reduce the drug doses to avoid severe side effects in patients with chronic treatment.…”

Section: Introductionmentioning

confidence: 99%

Activation of Peripheral Cannabinoid Receptors Synergizes the Effect of Systemic Ibuprofen in a Pain Model in Rat

et al. 2022

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Pharmacological synergism is a current strategy for the treatment of pain. However, few studies have been explored to provide evidence of the possible synergism between a non-steroidal anti-inflammatory drug (NSAID) and a cannabinoid agonist, in order to establish which combinations might be effective to manage pain. The aim of this study was to explore the synergism between ibuprofen (IBU) and the synthetic cannabinoid WIN 55,212-2 (WIN) to improve pain relief by analyzing the degree of participation of the CB1 and CB2 cannabinoid receptors in the possible antinociceptive synergism using an experimental model of pain in Wistar rats. First, the effective dose thirty (ED30) of IBU (10, 40, 80, and 160 mg/kg, subcutaneous) and WIN (3, 10, and 30 µg/p, intraplantar) were evaluated in the formalin test. Then, the constant ratio method was used to calculate the doses of IBU and WIN to be administered in combination (COMB) to determine the possible synergism using the isobolographic method. The participation of the CB1 and CB2 receptors was explored in the presence of the antagonists AM281 and AM630, respectively. The combination of these drugs produced a supra-additive response with an interaction index of 0.13. In addition, AM281 and AM630 antagonists reversed the synergistic effect in 45% and 76%, respectively, suggesting that both cannabinoid receptors are involved in this synergism, with peripheral receptors playing a relevant role. In conclusion, the combination of IBU + WIN synergism is mainly mediated by the participation of the CB2 receptor, which can be a good option for the better management of pain relief.

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The Role of Organic Small Molecules in Pain Management

Cited by 12 publications

References 152 publications

Food-Specific IgG4 Antibody-Guided Exclusion Diet Improves Conditions of Patients with Chronic Pain

Food-Specific IgG4 Antibody-Guided Exclusion Diet Improves Conditions of Patients with Chronic Pain

Synergistic Antinociceptive Effects of Indomethacin–Pregabalin and Meloxicam–Pregabalin in Paclitaxel-Induced Neuropathic Pain

Activation of Peripheral Cannabinoid Receptors Synergizes the Effect of Systemic Ibuprofen in a Pain Model in Rat

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