Hyperalgesia

An injured area is typically more sensitive to subsequent stimuli. As a result, painful stimuli, or even normally nonpainful stimuli, may cause an excessive pain response. An increase in the sensitivity of nociceptors is referred to as primary hyperalgesia. A classic example of hyperalgesia is a bum. Even light touch of a burned area may be painful. 

Centrally mediated hyperalgesia involves the hyperexcitability of second-order sensory neurons in the dorsal horn of the spinal cord. In the case of severe or persistent tissue injury, C fibers fire action potentials 

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Increased responsiveness to noxious stimuli is termed hyperalgesia. It occurs following injury or disease and encompasses enhanced responses as well as reduced thresholds to a given noxious stimulus. Primary hyperalgesia occurs in the damaged area whereas secondary hyperalgesia occurs in the area surrounding it. 

Clinical manifestation Primary hyperalgesia, allodynia, spontaneous pain Secondary hyperalgesia, allodynia, spontaneous pain, aberrantly referred pain ... 

Nociceptive neurons in the spinal cord as well as in higher centres such as the thalamus and cortex can also undergo alterations in activity following chronic peripheral changes and trauma (Table 1). These changes are typically long-term in nature and lead to the clinical syndromes of centrally maintained pain (secondary hyperalgesia, allodynia, spontaneous pain). Alterations... 

Garcia-Martinez, C., Humet, M., Pla-nells-Cases, R., Gomis, A., Caprini, M., ViANA, F., Pena, E. D., Sanchez-Baeza, F., Carbonell, T, Felipe, C D., Perez-Paya, E., Belmonte, C., Messeguer, A., and Ferre-Montiel, A. Attenuation of thermal nociception and hyperalgesia by VRl blockers. Proc. Natl. Acad. Sci. USA 2002, 99, 2374-2379. 

Davis A, Perkins M The involvement of bradykinin B1 and B2 receptor mechanisms in cytokine-induced mechanical hyperalgesia in the rat. Br J Pharmacol 1994 113 63-68. 

Association of Pain, neuropathic pain is defined as pain initiated or caused by a primary lesion, dysfunction in the nervous system". Neuropathy can be divided broadly into peripheral and central neuropathic pain, depending on whether the primary lesion or dysfunction is situated in the peripheral or central nervous system. In the periphery, neuropathic pain can result from disease or inflammatory states that affect peripheral nerves (e.g. diabetes mellitus, herpes zoster, HIV) or alternatively due to neuroma formation (amputation, nerve transection), nerve compression (e.g. tumours, entrapment) or other injuries (e.g. nerve crush, trauma). Central pain syndromes, on the other hand, result from alterations in different regions of the brain or the spinal cord. Examples include tumour or trauma affecting particular CNS structures (e.g. brainstem and thalamus) or spinal cord injury. Both the symptoms and origins of neuropathic pain are extremely diverse. Due to this variability, neuropathic pain syndromes are often difficult to treat. Some of the clinical symptoms associated with this condition include spontaneous pain, tactile allodynia (touch-evoked pain), hyperalgesia (enhanced responses to a painful stimulus) and sensory deficits. 

Analgesia Relief of anxiety Euphoria Nausea Constipation Cough suppression Dependence Similar to mu but less marked Analgesia Aversion Diuresis Analgesia Hyperalgesia... 

Studies with TRPVl-deficient animals confirmed the pivotal role that this receptor plays in the development of postinflammatory hyperalgesia [15, 16]. Now there is good evidence that TRPVl expression is regulated in humans. As of 2005, diseases with up-regulated TRPVl include inflammatory bowel... 

Compared to wild-type mice, in TRPVl gene-deleted (—/—) mice, complete Freund s adjuvant evokes significantly less oedema, hyperalgesia and arthritis score [149]. 

Novartis AG has filed a patent application on novel naphthalene derivatives as potent cannabinoid agonists, especially at the CBi receptor [208]. One compound was specifically claimed, the naphthalene derivative (319), which exhibited CBi binding with a if value of 15 nM. This compound was also active in an in vivo model of neuropathic pain, reversing hyperalgesia... 

Hyperalgesia An increased pain response to a stimulus that normally causes pain. 

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