Peripheral analgesia

M, Supraspinal analgesia, peripheral analgesia, euphoria, prolartin release ... 

CCK is found in the digestive tract and the central and peripheral nervous systems. In the brain, CCK coexists with DA. In the peripheral nervous system, the two principal physiological actions of CCK are stimulation of gaU. bladder contraction and pancreatic enzyme secretion. CCK also stimulates glucose and amino acid transport, protein and DNA synthesis, and pancreatic hormone secretion. In the CNS, CCK induces hypothermia, analgesia, hyperglycemia, stimulation of pituitary hormone release, and a decrease in exploratory behavior. The CCK family of neuropeptides has been impHcated in anxiety and panic disorders, psychoses, satiety, and gastric acid and pancreatic enzyme secretions. 

Local anaesthetics are drugs that reversibly interrupt impulse propagation in peripheral nerves thus leading to autonomic nervous system blockade, analgesia, anaesthesia and motor blockade in a desired area of the organism. 

A high concentration of DOPs is found in the olfactory bulb, the neocortex, caudate putamen, and in the spinal cord, but they are also present in the gastrointestinal tract and other peripheral tissues. The functional roles of DOP are less clearly established than for MOP they may have a role in analgesia, gastrointestinal motility, mood and behaviour as well as in cardiovascular regulation [2]. 

They act as analgesics by inhibiting release of nociceptive neurotransmitters from primary afferent terminals as well as by depressing post-synaptic potentials on second order neurons. Opioid receptors are also present on some nociceptors and their expression and peripheral transport is increased upon peripheral inflammation. Peripheral opioid analgesia has been established in animal models. Although clinical studies have yielded mixed results so far, this field holds great promise. Despite side effects, such as euphoria, dysphoria, sedation, respiratory depression and obstipation and tolerance and dependence phenomena which arise upon... 

An intriguing area of research on opioids has been the accumulating evidence for plasticity in opioid controls. The degree of effectiveness of morphine analgesia is snbject to modulation by other transmitter systems in the spinal cord and by pathological changes induced by peripheral nerve injury. Thus in neuropathic states, pain after nerve injury, morphine analgesia can be reduced (but can still be effective) and tactics other than dose-escalation to circumvent this will be briefly discussed in Chapter 21. 

Malan TP Jr, Ibrahim MM, Deng H, Liu Q, Mata HP, Vanderah T, Porreca F, Makriyannis A. CB2 cannabinoid receptor-mediated peripheral analgesia. Pain In press. 

Similar to tobacco, lobelia may also have analgesic effects. However, it depends on the mode of administration (Damaj et al. 1997). Intrathecal lobeline produces analgesia on the tail-flick test, but subcutaneous administration is ineffective. On the other hand, subcutaneous lobeline dose-dependently enhances nicotine analgesia. Tolerance develops to this effect of lobeline after 10 days. Lobeline can also produce hyperalgesic effects when administered into the dorsal posterior mesencephalic tegmentum (Hamann and Martin 1994). However, the relevance of this to peripheral administration of lobelia is questionable because chronic injections (IP) of lobeline in rats induced no changes in tail-flick latencies (Sopranzi et al. 1991). 

Mectianism of Action An antiadrenergic, sympatholytic agent that prevents pain signal transmission to the brain and produces analgesia at pre- and post-alpha-adrenergic receptors in the spinal cord. Therapeutic Effect Reduces peripheral resistance decreases BP and heart rate. 

Analgesic action Salicylates relieve pain by both central and peripheral action. The site of action of central analgesia seems to be the hypothalamus. It does not have cortical action on the reaction component of the pain but raises the threshold to pain perception. Unlike morphine, they do not produce sedation and there is no drug tolerance or dependence and are not effective against visceral pain. 

It is a para-amino phenol derivative, acts on CNS to produce analgesia and antipyretic effect. It has negligible antiinflammatory action peripherally in therapeutic uses. It is poor inhibitor of PG synthesis in peripheral tissues, but more active on COX in brain. It also raises the pain threshold. 

An anatomic circumstance that sometimes creates exceptions to the above rules for differential nerve block is the location of the fibers within the peripheral nerve bundle. In large nerve trunks, fibers located circumferentially are the first to be exposed to the local anesthetic when it is administered into the tissue surrounding the nerve. In the extremities, proximal sensory fibers are located in the outer portion of the nerve trunk, whereas the distal sensory innervation is located in the central core of the nerve. Thus, during infiltration block of a large nerve, sensory analgesia first develops proximally and then spreads distally as the drug penetrates deeper into the core of the nerve. 

Opioid agonists produce analgesia by binding to specific G protein-coupled receptors that are located in brain and spinal cord regions involved in the transmission and modulation of pain (Figure 31-1). Some effects may be mediated by opioid receptors on peripheral sensory nerve endings. 

---