Paracetamol for low back pain: the state of the research field
EXPERT REVIEW OF CLINICAL PHARMACOLOGY
Authors: Koes, Bart; Schreijenberg, Marco; Tkachev, Alexander
Abstract
Introduction Paracetamol is one of the most frequently used analgesics for people with low back pain, but despite its frequent use there is still debate regarding its efficacy and safety for this indication. Areas covered We describe the origin of paracetamol and its proposed mechanisms of action. We focus in on low back pain and describe the evidence it has on the efficacy of paracetamol (taken by patients orally) and current insights on its side-effects. When searching for relevant publications we focused mainly on recent Cochrane reviews and published RCTs. We found that there is increasing evidence that shows paracetamol is not more effective than placebo in patients with acute low back pain. Concerning patients with subacute and chronic back pain, the evidence for or against the efficacy of paracetamol vs placebo is lacking and would need more research. Expert opinion We argue that we still need better evidence on the efficacy of paracetamol for acute and chronic back pain. Until that evidence becomes available paracetamol should still be considered as an option for patients with back pain. However, we suggest that a strategy focusing on non-pharmacological management as the first treatment option in low back pain may be equally effective with less side effects.
N-acetyl-cysteine in combination with celecoxib inhibits Deoxynivalenol induced skin tumor initiation via induction of autophagic pathways in swiss mice
FREE RADICAL BIOLOGY AND MEDICINE
Authors: Mishra, Sakshi; Divakar, Aman; Srivastava, Sonal; Dewangan, Jayant; Sharma, Divyansh; Asthana, Somya; Chaturvedi, Swati; Wahajuddin, Muhammad; Kumar, Sadan; Rath, Srikanta Kumar
Abstract
Deoxynivalenol is a trichothecene mycotoxin which naturally contaminates small grain, cereals intended for human and animal consumption. Investigations for dermal toxicity of DON has been needed and highlighted by WHO. Previous studies on dermal toxicity suggest that DON has DNA damaging potential leading to skin tumor initiation in mice skin. However, considering its toxicological manifestations arising after dermal exposure, strategies for its prevention/protection are barely available in literatute. Collectively, our study demonstrated that N-acetylcysteine (NAC), precursor of glutathione, significantly alters the genotoxic potential of DON. Further NAC in combination with Celecoxib (CXB) inhibits tumor growth by altering antioxidant status and increasing autophagy in DON initiated Swiss mice. Despite the broad spectrum use of CXB, its use is limited by the concerns about its adverse effects on the cardiovascular system. Serum parameters and histology analysis revealed that CXB (2 mg) when applied topically for 24 weeks did not impart any cardiovascular toxicity which could be because skin permeation potential of CXB was quite low when analyzed through HPLC analysis. Although the anticancer effects of CXB and NAC have been studied, however, the combination of NAC and CXB has yet not been explored for any cancer treatment. Therefore our observations provide additional insights into the therapeutic effects of combinatorial treatment of CXB and NAC against skin tumor prevention. This approach might form a novel alternative strategy for skin cancer treatment as well as skin associated toxicities caused by mycotoxins such as DON. This combinatorial approach can overcome the limitations associated with the use of CXB for long term as topical application of the same seems to be safe in comparison to the oral mode of administration.