Local anesthetics additive analgesic effects

Neostigmine offers additive analgesic effects when combined with opioids and alpha-2-adrenoceptor agonists such as clonidine. Opioids and NE receptors modulate pain via descending inhibitory fibers, whereas Ach receptors are suppressive at local interneurons. This addition of local modulation of noxious transmission may explain the opioid and local anesthetic sparing potential of neostigmine. 

Oxolamine [959-14-8] (57) is sold in Europe. It is an oxadiazole, and its general pharmacological profile is described (81). The compound possesses analgesic, antiinflammatory, local anesthetic, and antispasmodic properties, in addition to its antitussive activity. Although a central mechanism may account for some of the activity, peripheral inhibition of the cough reflex may be the dominant effect. The compound has been shown to be clinically effective, although it is less active than codeine (82,83). The synthesis of oxolamine is described (84). 

Additions of 1/10 to 2 1/2% of urea to dilute procaine solutions increase materially their potency, to ten times, on direct application to nerve trunks, presumably by favoring penetration. The effect is not due to alkalinization. The action of local anesthetics is reported to be increased by intravenous injection of methylene blue, by the local application of caffeine or theophylline, by morphine, and by the antipyretic analgesics. Cocaine anesthesia is said to be ineffective in tissue impregnated with oxalic acid. Inflamed tissues are less susceptible to local anesthesia, probably because of their difficult penetration. 

The addition of fentanyl to the local anesthetic prilocaine does not seem to cause major analgesic benefits, but increases the incidence of adverse effects, particularly affecting the nervous system (82). 

Intradermal local anesthetic solutions can cause considerable pain on injection. Additives, such as hyaluronidase, which are used to enhance the analgesic effect of local anesthetics, can often exacerbate this (165). Infiltration from the inside of a wound can be less painful than through intact skin (166). 

Phenol is a benzyl alcohol and a major oxidized metabolite of benzene that was introduced into medicine as an antiseptic (1). Although it can be prepared in an aqueous solution or in glycerine, it appears to be more effective when mixed in aqueous compounds. At a concentration of 0.2% it is bacteriostatic and at over 1% bactericidal (2). In addition to its uses as an antiseptic and disinfectant, phenol is also used as a sclerosant, as a local anesthetic on the skin, and as an analgesic, by injection into nerves or spinally, but its use was limited by severe adverse effects. Current medical uses include cosmetic face peeling, nerve injections, and topical anesthesia. It is also an ingredient of various topical formulations, and is used as an environmental disinfectant. 

The addition of epidural sufentanil to local anesthetics significantly potentiates their analgesic effects. They also provide for safe and effective analgesia at a lower concentration and dose of local anesthetics. As a result this decreases the incidence of side effects such as motor blockade and hypotension. 

There is an additive anesthetic effect when combining local anesthetics with opioid analgesics. There are well-documented spinal opioid receptors in the dorsal horn, and up-regulation of opioid receptors has been described in chronically inflamed peripheral nerves. 

The addition of morphine and fentanyl to intrathecal and epidurally administered local anesthetics decreases local anesthetic dose requirements while reducing surgical and post-operative pain intensity. One exception is chloroprocaine, which may antagonize epidural opioid analgesic effects. 

Although continuous infusion is the most popular means of administration, it is generally associated with sensory block regression, notably with local anesthetic alone. The time to first analgesic rescue is increased by addition of opioid. The long-known popularity of infusion is the result of the perception that the cardiovascular and respiratory side-effects of it are less when compared to with bolus alone (11). 

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