Nociception structures

Afferent input from cutaneous and visceral nociceptors is known to converge on spinal neurons, which accounts for the referral of pain between visceral and cutaneous structures (e.g. cardiac pain gets referred to the chest and left upper arm in patients suffering from angina pectoris). Projection neurons in the spinal dorsal horn project to cell nuclei in supraspinal areas such as the thalamus, brainstem and midbrain. Of these, the synaptic junctions in the thalamus play a very important role in the integration and modulation of spinal nociceptive and non-nociceptive inputs. Nociceptive inputs are finally conducted to the cortex where the sensation of pain is perceived (Fig. 1). The mechanisms via which the cortex processes nociceptive inputs are only poorly understood. 

V.c.1.1. Cyclo-oxygenase inhibition. Inhibition of cyclo-oxygenase reduces the level of circulating prostaglandins and neurogenic inflammation. This is the mechanism of action of nonsteroidal antiinflammatory drugs (NSAID) and aspirin. The mode of action of paracetamol is less clear (inhibition of prostaglandins in the nociceptors of the posterior horn of the spinal cord and action on the supraspinal structures implicated in nociception). 

Evidence from experimental pain research has revealed that mGluRs play a pivotal role in nociceptive processing, inflammatory pain and hyperalgesia. mGluRs have been implicated in dorsal horn neuronal nociceptive responses and pain associated with short-term inflammation (Neugebauer 2002) as well as its emotional component involving hmbic structures such as the amygdala (Han et al. 2004). 

Antilipidemic activity. Triglycerides structured lipids from coconut oil, administered to rats at a dose of 10% of diet for 60 days, produced a 15% decrease in total cholesterol and a 23% decrease in LDL cholesterol levels in the serum compared to coconut oil-fed rats. Total and free cholesterol levels in the liver of structured lipid-fed rats were lowered by 31 and 36%, respectively. The triglycerides in the serum and liver were decreased by 14 and 30%, respectively " . Anti-nociceptive activity. Aqueous extract of the husk fiber, administered orally to mice at doses of 200 or 400 mg/kg, produced an inhibition of the acetic acid-induced writhing response . 

Skeletal muscle spasms are used to describe the increased tension often seen in skeletal muscle after certain musculoskeletal injuries and inflammation (muscle strains, nerve root impingements, etc.) occur.20,96 This tension is involuntary, so the patient is unable to relax the muscle. Spasms differ from spasticity because spasms typically arise from an orthopedic injury to a musculoskeletal structure or peripheral nerve root rather than an injury to the CNS. Likewise, muscle spasms are often a continuous, tonic contraction of specific muscles rather than the velocity-dependent increase in stretch reflex activity commonly associated with spasticity. The exact reasons for muscle spasms are poorly understood. According to some authorities, muscle spasms occur because a vicious cycle is created when the initial injury causes muscular pain and spasm, which increases afferent nociceptive input to the spinal cord, further exciting the alpha motor neuron to cause more spasms, and so on.61,96 Other experts believe that muscle spasms occur because of a complex protective mechanism, whereby muscular contractions are intended to support an injured vertebral structure or peripheral joint.96 Regardless of the exact reason, tonic contraction of the affected muscle is often quite painful because of the buildup of pain-mediating metabolites (e.g., lactate). 

Prokineticin receptors are potential targets for drugs which block the nociceptive information before it reaches the brain. Identifying of the structural determinants required for receptor binding and hyperalgesic activity of Bv8-Prokineticins... 

Gatch MB, Negus SS, Mello NK, Archer S, Bidlack JM (1996) Effects of the structurally novel opioid 14 alpha, 14 beta-[dithiobis[(2-oxo-2,l-ethanediyl)imino]]bis(7,8-dihydromor-phinone) schedule-controlled behavior and thermal nociception in rhesus monkeys. J Pharmacol Exp Ther 278 1282-1289... 

Nociceptive pain typically is classified as either somatic (arising from skin, bone, joint, muscle, or connective tissue) or visceral (arising from internal organs such as the large intestine or pancreas). While somatic pain most often presents as throbbing and well localized, visceral pain can manifest as pain feeling as if it is coming from other structures (referred) or as a well-localized phenomenon. We can think of nociception in terms of stimulation, transmission, perception, and modulations (Table 58-1). 

The puzzle of how one ion channel could be activated by such a broad range of irritants (e.g., AITC, formalin, alUcin, diaUyl disulfide, acrolein, cinnamaldehyde) with minimal structural similarity was reconciled by the discovery that TRPAl is activated when electrophiles form covalent adducts with three cysteines (and, in human TRPAl, one lysine) within the channel s cytosolic N terminus (Hinman et al. 2006 Macpherson et al. 2007a). This suggests that any cysteine-reactive electrophile that can access these crucial residues has the potential to activate TRPAl and evoke nociceptive reflexes. In support of this, iodoacetamide, the cysteine-reactive tool molecule often used in biochemical experiments, activates TRPAl (albeit with very low potency) and evokes nocifensive behaviors in wild-type but not TRPAl knockout mice (Macpherson et al. 2007b). 

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