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As noted previously in this Journal, the provision of pain relief is a basic tenet of health care which should concern all relevant professionals, purchasers and policy makers (Cowan, 2007). It was also noted that pain is under-treated in the UK (Davies and McVicar, 2000) and that the economic burden of chronic non-cancer pain (CNCP) is high (Reginster, 2002). These disorders, such as OA are associated with the poorest quality-of-life issues, and the prevalence of OA is expected to increase as this affects older people, who constitute an increasing proportion of the population (Reginster, 2002). Pain among older people is a significant problem and more evidence to inform prescribing, particularly CNCP, is required (Cowan 2002). These issues remain unresolved.
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Osteoarthritis pain

For some time, people have not been satisfied with approaches to managing OA pain (Jay et al, 1997; Arthritis News, 2000; Cowan, 2007; Arthritis Research Campaign (ARC), 2009a). In addition, little evidence exists to inform prescribing practices regarding the safety and efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) in older people and indeed for the whole spectrum of age groups (Cowan, 2002; 2007). NSAIDs are one of the most widely used groups of drugs in England, particularly for OA among older people (Department of Health (DH), 2001; Jones et al, 2002). However, it has long been apparent that traditional NSAIDs are not suitable for many people who are affected by OA, ironically, older people in particular (Cowan, 2002; 2007). In an age of evidence-based practice, we need information that will increase the overall knowledge base regarding medicines that have long been in common use, about which much is assumed, yet, about which relatively little is still known (Cowan, 2007). While previous papers in this Journal have focused on the need for such research into the use of comparing NSAIDs with opioid analgesics for CNCP (Cowan, 2002; 2007), this paper focuses on the suggestion that Aloe vera could be used in the treatment of such conditions, particularly pain caused by OA.
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Aloe vera has been used for medicinal purposes by humankind for centuries, including for the treatment of burns, as an anti-viral, for inhibition of tumour cells and not least, for treatment of arthritis (Yoo et al, 2008). Despite this, generally, the evidence for the effectiveness of Aloe vera is anecdotal or from relatively small studies. However, this evidence warrants further investigation. Authors have commented on Aloe vera’s anti-inflammatory properties when both applied topically and ingested orally (Atherton 1997; Davis, 1997). Furthermore, the findings of pre-clinical and animal studies also support the suggestion that Aloe vera is an efficacious anti-inflammatory agent (Yagi and Takeo, 2003; Yoo et al 2008). Yagi and Takeo (2003) found in an in vitro study that the neutral polysacchar ides of the Aloe species, aloemannan and acemannan demonstrated anti-inflammatory, anti-tumour and immuno-suppressive activities. When examining whether ethanol fractions of Aloe vera demonstrated in vitro anti-inflammatory activities, Yoo et al (2008) found that they potently suppressed the expression of cyclo-oxygenase (COX-2), which is identical to an anti-inflammatory mechanism of NSAIDs. Furthermore, in the in vivo arm of their study, Yoo et al (2008) demonstrated a statistically significant improvement in the analgesic effect among rats injected with Aloe vera as compared to controls (n=20, <0.05).
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Atherton (1997) found in an ‘n of 1’ study that a patient suffering from juvenile rheumatoid arthr itis and who was experiencing the abdominal side effects of ceiling NSAID doses was able to reduce NSAID use by half within an 18 month period of drinking Aloe vera gel.

In a small uncontrolled study by Blitz et al (1963) 12 patients (age range 24-84, male 70%), clinically diag- nosed by x-ray as having evidence of duodenal lesions, were treated with oral Aloe vera gel emulsion. Within a year, repeat x-ray examination indicated evidence of complete healing in 11 patients. The 84-year-old patient unfortunately died, but without recurrence of any lesion.
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Obviously, the above evidence needs to be augmented with more robust investigation. In vitro and animal work needs to be demonstrated and indeed replicated in statisti- cally significant samples of humans that are representative of the demographic profiles of those people who are most likely to benefit from var ious types of Aloe vera treatment. Thus, more rigorous, properly designed randomized, controlled, large scale studies are now needed. However, despite the apparent shortcomings of the current evidence, the perceived benefits of prescribing Aloe vera for people with OA can be seen as twofold: Aloe vera has utility as an anti-inflammatory agent and also as a prophylactic against the detrimental gastrointestinal irritant effects of NSAIDs.
Clearly, an agent that can provide additional analgesic and anti-inflammatory effects for people with OA would constitute a major breakthrough in the treatment of this potentially debilitating disease. However, the additional benefit of protection against gastrointestinal damage is also of particular importance. NSAID-induced gastrointestinal toxicity has long been among the most common drug- related serious adverse events in industrialized nations (Fries, 1991). NSAIDs kill some 16500 Americans each year, making these drugs the fifteenth largest cause of death in the USA (New Scientist, 2005). In the UK, an estimated 12000 episodes of bleeding gastrointestinal ulcer and 2600 deaths are caused annually by NSAIDs (Moore and Phillips, 1999).
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The implications are significant. Aloe vera could be used as an anti-inflammatory agent either alone or in combination with other drugs, particularly NSAIDs. In the case of the latter, any gastro-protective effect against the damage caused by NSAIDs would be of considerable benefit, both in terms of quality of life and cost effectiveness.However, as previously noted, long-term, randomized, controlled studies of pain medications are still needed to address the problem of lack of available evidence to inform the optimum prescribing of pain medication for people with OA (Cowan, 2007). This applies equally to Aloe vera. There has been a trend for some time in resorting to complementary medicines, with many people suffering with pain caused by OA trying unproven supplements, with few of these having been convincingly shown to work. Indeed, a recent report by the Arthritis Research Campaign on complementary medicines in the use of arthritis found no randomized controlled trials involving the use of Aloe vera (ARC, 2009b). There is no reason though that so-called ‘nutraceutical’ agents should not be subjected to the same rigorous randomized, controlled, double-blind trials that other ‘mainstream’ drugs are subjected to. For example, research could be undertaken that focuses on comparing treatment for OA comprising an oral NSAID against an oral NSAID combined with an oral Aloe vera adjuvant. It is possible that the quality of life of OA sufferers could be improved by more effective analgesia and attenuation of NSAID side effects afforded by the addition of Aloe vera. Furthermore, it may be that in some cases, Aloe vera could replace NSAIDs.
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While OA affects several million people in the UK, many of them older people, there is currently no cure for this condition, so the emphasis has to be on effective treatment. Current drug treatments to relieve pain caused by OA are unsatisfactory with many people experiencing dif- ficulty in finding an agent that affords adequate pain relief with no side effects (Cowan, 2007). Data derived from the proposed research would help to inform optimum prescribing for people with OA. The growing acceptance of alternative therapies and the acknowledged severity of NSAID side effects make it appropriate to now ask whether NSAID treatment and associated side effects can be improved by the addition of Aloe vera or indeed, even replaced by it. Thus, we may then be in a more informed position to resolve the ongoing ‘Pandemonium over Painkillers’ (Arthritis News, 2000; Cowan, 2007).
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