Articles: hyperalgesia.
-
Cold allodynia is a common sign of neuropathic pain patients but its underlying mechanisms are still largely unknown, partly because the populations of neurons responding to cold stimuli and their transduction mechanisms have not been fully determined. We report a patient with a small-fiber neuropathy of unknown origin, whose main complaint is cold allodynia. ⋯ These findings provide the first direct evidence in human of abnormal peripheral nociceptor behavior potentially responsible for cold allodynia. The responsiveness of C-nociceptors to menthol suggests an abnormal expression or function of TRPM8 channels in this patient with a small-fiber polyneuropathy.
-
Although evidence shows that several dopamine neurotransmission pathway genes are associated with specific clinical pain syndromes, such as fibromyalgia, chronic headache, and postoperative pain, the exact role of dopamine in pain processing is not fully understood. The aim of this study was to explore the relationship between functional polymorphisms in dopaminergic candidate genes and sensitivity to pain in healthy subjects. Healthy subjects (n=192; 105 F, 87 M) were exposed to experimental tonic cold pain (1 degrees C) and phasic heat pain (47 degrees C) stimuli. ⋯ Significant associations between cold pain tolerance and DAT-1 (p=0.008) and MAO-A (p=0.024) polymorphisms were found. Specifically, tolerance was shorter for carriers of allele 10 and the rarer allele 11, as compared to homozygous for allele 9, and for carriers of allele 4 as compared to homozygous for allele 3, respectively. These results, together with the known function of the investigated candidate gene polymorphisms, suggest that low dopaminergic activity can be associated with high pain sensitivity and vice versa.
-
Both pro-nociceptive and antinociceptive mediators are released in the tissues during inflammation. Balance of these two types of mediators determines the induction and maintenance of pain or hypernociception. This study was designed to explore whether 5-HT(2A) receptors in the periphery contributed to the maintenance of carrageenan-evoked hyperalgesia. ⋯ The hypoalgesia was completely abolished by local or systemic injection of naloxone methiodide. The present study suggests that 5-HT(2A) receptors were involved in the maintenance of inflammatory pain, and that 5-HT suppressed inflammation-associated endogenous opioid analgesia contributing to its pro-nociceptive actions in the periphery. It implied a possible therapeutic benefit of blockade of local 5-HT(2A) receptors in the treatment of inflammatory pain.
-
Randomized Controlled Trial Clinical Trial
Analgesic efficacy of tramadol, pregabalin and ibuprofen in menthol-evoked cold hyperalgesia.
We investigated the analgesic efficacy of single doses of ibuprofen, tramadol and pregabalin in menthol-evoked cold pain in a randomized, placebo-controlled four-way cross-over study in 20 healthy volunteers. Tramadol 100mg significantly reduced menthol-evoked cold hyperalgesia. Effects of ibuprofen 600mg and pregabalin 100mg were not significant. ⋯ Minor side effects also accompanied analgesic effects of pregabalin and ibuprofen in subjects responding to these drugs, mostly fatigue, dizziness and difficulties to concentrate for pregabalin and gastric upset for ibuprofen. Five out of 18 subjects had a 50% reduction of cold hyperalgesia with tramadol, three of these additionally responded to pregabalin, and two with all three drugs. The numbers needed to treat (NNT >or= 50% for tramadol 4.5, for pregabalin 9) largely agree with the reported efficacy of tramadol and of moderate dosages of pregabalin in patients with peripheral or central neuropathic pain suggesting that menthol-evoked cold pain hypersensitivity may represent a valid model for neuropathic pain, particularly cold allodynia.
-
Pain in early life can enhance the response to subsequent injury, but effects are influenced by both the nature and timing of neonatal injury. Using plantar hindpaw incision, we investigated how postnatal age influences the response to repeat surgical injury two weeks later. The degree and time course of behavioural changes in mechanical withdrawal threshold were measured, and injury-related hyperalgesia was further quantified by flexion reflex electromyographic responses to suprathreshold mechanical stimuli 24 h following incision. ⋯ Repeat peri-operative, but not a single pre-operative sciatic block, prevented the enhanced response to repeat incision two weeks later. Our results show that the first postnatal week represents a critical period when incision increases hyperalgesia following repeat surgery two weeks later, and effects are initiated by peripheral afferent activity. This has potential therapeutic implications for the type and duration of peri-operative analgesia used for neonatal surgery.