Effects on Inflammation

Capsaicin desensitization abolished dye leakage in response to a host of agents thought to act on sensory endings but failed to inhibit the inflammatory response produced by substances such as compound 48/80 

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Acetaminophen, another alternative to aspirin, is an effective analgesic and fever-reducing agent. However, this medication has no effect on inflammation. 

Local anesthetics have poorly understood effects on inflammation at sites of injury, and these anti-inflammatory effects may contribute to improved pain control in some chronic pain syndromes. At the concentrations used in spinal anesthesia, local anesthetics can inhibit transmission via substance P (neurokinin-1), NMDA, and AMPA receptors in the secondary afferent neurons (Figure 26-1). These effects may contribute to the analgesia achieved by subarachnoid administration. Local anesthetics can also be shown to block a variety of other ion channels, including nicotinic acetylcholine channels in the spinal cord. However, there is no convincing evidence that this mechanism is important in the acute clinical effects of these drugs. High concentrations of local anesthetics in the subarachnoid space can interfere with intra-axonal transport and calcium homeostasis, contributing to potential spinal toxicity. 

No more than 7 mg can be taken within 48 hours. It is a possible teratogen and produces a number of side effects such as Gl upset, peripheral neuritis, rashes, blood dyscrasias (bleeding, bruising, tiredness), lowers body temperature, induces hypertension, and so on. However, its effects on inflammation and swelling are dramatic and it can be extremely effective when given as a prophylactic and for beginning, acute attacks. 

Aspirin is most effective in reducing pain of mild to moderate intensity through its effects on inflammation and because it probably inhibits pain stimuli at a subcortical site. 

One compound that is not an NSAID but is often lumped into this group is acetaminophen (Tylenol, A.154) (Figure A.43). Acetaminophen is both an analgesic and suppresses fever but has no effect on inflammation and blood clotting. Acetaminophen also has less impact on the stomach lining than NSAIDs. Acetaminophen is believed to act both by COX inhibition as well as other pain response pathways. Unlike NSAIDs, acetaminophen acts on cannabinoid receptors. 

The in vivo assays for the Cox-2 inhibitors are essentially those used historically for NSAIDs to evaluate both their desired effects on inflammation, pain, and fever and their undesired effects, mainly on GI lesions. The primary in vivo assay for anti-inflammatory efficacy is the carrageenan-induced rat paw edema assay, and 51 Cr fecal excretion is used to test for damage to the intestinal mucosa in rats and in squirrel monkeys. Additional tests for efficacy are the endotoxin-induced pyresis in rats and squirrel monkeys for control of fever and the carrageenan-induced rat paw hyperalgesia assay for analgesic efficacy. These in vivo assays have been described (Chan et al., 1995 Chan et al., 1997). The rat... 

Genetically modified mice either overexpressing or knocking out specific components have provided exciting advances in our knowledge of diseases. Recently, we focused on the p38 mitogen-activated protein kinase (MAPK) pathway and its physiological effect on inflammation. 

Corticosteroids are commonly prescribed for moderate to severe Crohn s disease with short term efficacy probably related to their effect on inflammation. Anti-bacterials are commonly used as primary therapy in Crohn s disease. Common adverse effects of metronidazole are nausea and a metallic taste, hov ever peripheral neuropathy may result from long term use. Ciprofloxacin and similar antibacterials can be beneficial in those patients intolerant to mefi onidazole. 

Recall that aspirin blocks access to the active site of the enzyme that converts arachidonate into prostaglandin H-> (p. 339). Because arachidonate is the precursor of other prostaglandins, prostacyclin, and thromboxanes, blocking this step interferes with many signaling pathways. Aspirin s ability to obstruct these pathways accounts for its wide-ranging effects on inflammation, fever, pain, and blood clotting. 

Rothman D, DeLuca P, Zurier RB. Botanical lipids effects on inflammation, immune responses, and rheumatoid arthritis. Semin Arthritis Rheum 1995 25 87-96. 

Effects on inflammation and pain E- and F-series PGs are known to be released in the inflammation and increase capillary permeability, producing edema and painful erythema. PGE, can produce this in quantities as low as 1 (ig PGFla requires about 1 jig. Erythema produced by an intradermal application may persist for 10 h. There is evidence that PGs Ej, E2, A2, and F2ot stimulate (potentiate ) histamine and bradykinin. Low concentrations of PGs induce hyperalgesia. This appears to be a sensitization of pain receptors. It was also demonstrated that subdermal infusion of PGE only pro-... 

Gobel, R. J., Larsen, N., Jakobsen, M., Molgaard, C., Michaelsen, K. F. (2012). Probiotics to adolescents with obesity effects on inflammation and metabolic syndrome. Journal of Pediatric Gastroenterology and Nutrition, 55(6), 673-678. 

The latest mechanism via which gut bacteria have been shown to exert their effect on inflammation is via impact on regulatory T cells. Butyrate produced by commensal bacterial fermentation, as well as propionate, are reportedly able to promote regulatory T-cell generation in the colon, which are anti-inflammatory in nature. 

Olive oil has an effect on inflammation—olive oil decreases expression of VCAM-1 and interferes with activation of nuclear factor kB (NFkB) (96). 

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