Pain is an “unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”.
Acute pain is interpreted as an alarm signal related to actual or potential tissue damage—when pain persists it can become a serious condition in its own right. Usually, pain is caused by stimuli approaching or exceeding harmful intensity, but in the case of prolonged pain the sensitive feedback system is altered, and microglia cells are activated. Even if this hypothesis is not confirmed at clinical level, it could explain the relationships between the lack of inflammatory substances and the chronic pain and the central nervous system pain control failure. Chronic pain is defined as pain that persists for longer than three months. In patients with arthritis or other musculoskeletal conditions, pain is frequently triggered by inflammation of peripheral tissues (nociceptive pain), but it is also associated with a lesion (or dysfunction) of the nerve pathways (neuropathic pain). More often, nociceptive pain and neuropathic pain coexist particularly in patients with chronic back pain. Unfortunately, there is no universally recognised standard of care as there is a number of distinct pathological mechanisms of pain (acute or chronic) as well as a wide range of therapeutic options to manage patients with chronic pain including pharmacological and interventional treatments physical, psychological, complementary and alternative medicine approaches. In Europe nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-line therapy in the majority of patients with musculoskeletal pain in conjunction with nonpharmacological therapies, such as exercise, physiotherapy, acupuncture and herbal-based preparations. The high frequency of adverse events with NSAIDs—gastrointestinal toxicity, renal dysfunction, cardiovascular complications, and the risk of drug–drug interactions, particularly in older patients with comorbidities—in part explains the increasingly widespread use of “alternative” treatments. Local pharmacological therapy, if effective and well tolerated, represents an acceptable alternative to systemic NSAIDs.
Mesotherapy consists of a series of “microinjections” of drug/active substance into the dermis using short needles where the needle is positioned at an appropriate angle depending on the thickness of the skin. We suggest using a single needle, 4 mm (27 gauge) or 13 mm (30 or 32 gauge), positioned at 30–45 degree with respect to the skin surface. In general, 0.10–0.20 mL of product is used and injection points are usually 2 or 3 cm apart. If large areas are to be treated, the drug can be diluted, but this reduces the dosage, and, therefore, additional or more frequent injections are necessary. Following injection, the drug slowly reaches the underlying tissues achieving concentrations higher than those obtained with intramuscular administration. Interestingly, some authors consider mesotherapy as an intra- or subcutaneous technique; however, subcutaneously administered drugs may have different pharmacokinetics (diffusion and distribution) and as a result different onset and duration of activity depending on the site of injection. For example, plasma glucose levels vary depending on the subcutaneous site of injection—abdomen, arm, or leg—due to the level of absorption at the various injection sites. In contrast, injection into the superficial layer of the skin (intradermal) allows slow diffusion of the drug into the tissues underlying the site of injection. Sodium ketoprofen levels in skin, muscles, and joints following local intradermal or intramuscular (IM) have been measured in preclinical studies, and results show higher concentrations of the drug in skin, local muscles, and joints (corresponding the site of injection) following intradermal administration compared with following IM injection and these levels which remain high for longer than following IM administration. These results were confirmed with the intradermal inoculation of procaine and penicillin G. Similar results were demonstrated in human studies following intradermal injection (up to 4 mm), and interestingly results confirmed that when a drug is injected at a depth of more than 10 mm it remains for a short time in the surrounding tissues and reaches the systemic circulation rapidly.