Mechanisms inflammatory pain

The mechanisms of pain and the ability to control pain may vary in different pain states. This is of particular importance in consideration of a rational basis for the treatment of both inflammatory and neuropathic pain where the damage to tissue and nerve leads to alterations in both the peripheral and central mechanisms of pain signalling. In respect of existing drug therapies, this plasticity, the ability of the system to change in the face of a particular pain syndrome, explains the effectiveness of NSAIDs in inflammatory conditions and yet is also responsible for some of the limitations in the effectiveness of opioids in neuropathic pain. 

In this chapter we highlight the mechanisms and neurochemical basis for nociceptive pain as well as the pain that occurs clinically after tissue injury (inflammatory pain) or nerve damage (neuropathic pain). 

Clinical pain is characterized by the presence of spontaneous pain or hypersensitivity to pain-provoking stimuli. Hypersensitivity includes pain produced by low-intensity stimuli that normally only elicit an innocuous sensation (allodynia), or an exaggerated response to a noxious stimulus (hyperalgesia). There are two distinct forms of clinical pain, the pain that occurs after tissue injury or inflammatory diseases (inflammatory pain) and the pain associated with a lesion or disease of the nervous system (neuropathic pain). Although the mechanisms responsible for the initiation and maintenance of these pains differ, they are both characterized by heightened... 

The opioids modulate the immune system by effects on lymphocyte proliferation, antibody production, and chemotaxis. In addition, leucocytes migrate to the site of tissue injury and release opioid peptides, which in turn help counter inflammatory pain. However, natural killer cell cytolytic activity and lymphocyte proliferative responses to mitogens are usually inhibited by opioids. Although the mechanisms involved are complex, activation of central opioid receptors could... 

Animal models of nociception can be divided according to the therapeutic indication Acute Pain, Migraine Pain, Inflammatory Pain, Visceral Pain, Neuropathic Pain. Different degrees of chronification (up to weeks in neuropathic pain models) and different stimuli (mechanical, thermal, chemical, electrical) are used depending on the experimental question. In most cases a nociceptive threshold (e g. withdrawal latency of a paw) is determined. Sometimes, nociceptive intensities are determined e.g. in order to quantify hyperalgesia. 

While the antinociceptive effect exerted by linalool has been extensively investigated in inflammatory pain, no studies exist on the effects of linalool in models of neuropathic pain. To this aim, we used the spinal nerve ligation (SNL) model of neuropathic pain (Kim and Chung, 1992) and studied the effects of acute and chronic administration of (—)-linalool on mechanical and thermal hypersensitivity induced by nerve injury in mice. 

Systemic administration of linalool showed antinociceptive effects in several models of inflammatory pain (Peana et al., 2003, 2004b). Here, we show for the first time that linalool is able to reduce mechanical allodynia in mice following SNL, a widely studied and recognized model of neuropathic pain. 

The antinociceptive effects are produced by peripheral, spinal and supraspinal levels as well (Przewlocki et al., 1999). ICV or intrathalamic administration of EMs produced antinociception in both acute and chronic pain models (Zadina et al., 1997 Zhao et al., 2007 Zubrzycka et al., 2005 Zubrzycka and Janecka, 2008). The EMs displayed lower potencies in the mechanical (paw pressure) test than in the heat-pain (TE) test in rats after IT administration (Horvath et al., 1999 Przewlocka et al., 1999), but they exerted high analgesic potency in different inflammatory pain... 

NAGly has been intensively studied (see Section 6.1.3), but only one report has investigated the antinociceptive potency of NAGABA and NAAla. It has been found that their IT administration does not produce an increase in mechanical and thermal pain threshold in the inflammatory pain model (Succar et al.,... 

A number of in vivo pharmacological studies reported that amino acid substitution in position 6 of 14-O-methyloxymorphone (48) afforded derivatives 55-60 that produce potent antinociceptive actions via peripheral mechanisms after s.c. administration in different pain models such as acute nociception i.e. tail-flick test [68], inflammatory pain i.e. formalin test [68] and carrageenan-induced hindpaw inflammation [75] and visceral pain i.e. acetic acid-induced writhing test [93]. In the tail-flick test in the rat, the 6-amino acid derivatives were 19- to 209-fold more potent than morphine (Table 7) and showed similar potency to fentanyl after s.c... 

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