Unity vs. diversity of neuropathic pain mechanisms: Allodynia and hyperalgesia in rats selected for heritable predisposition to spontaneous pain.
Do contrasting neuropathic pain diagnoses share common pathophysiological mechanisms? Selective breeding was used to derive rat lines with a common genetic background but a striking difference in the degree of spontaneous pain behavior expressed in the neuroma model of neuropathic pain (HA rats (high autotomy) and LA rats (low autotomy)). The contrasting pain phenotype in these lines is attributable to allelic differences at a small number of genetic loci. Here we show that HA and LA rats also differ in their nocifensive response to applied stimuli in the Chung (spinal nerve ligation, SNL) model of neuropathic pain. This includes tactile allodynia and hyperalgesia, and heat allodynia. The degree of hypersensibility varied with sex, age at the time of nerve injury, and the extent of the nerve lesion. F1 crosses of HA and LA rats and inbred Lewis rats showed low levels of autotomy but variable levels of hypersensibility to applied stimuli. Results indicate that alleles which predispose to spontaneous neuropathic pain also predispose to stimulus-evoked pain (allodynia and hyperalgesia). This, in turn, suggests that despite contrasting etiology and behavioral endpoints, pain phenotype in the neuroma and the SNL models shares common pathophysiological mechanisms.
Ziv-Sefer
Sagit
S
Dept. Cell and Developmental Biology, Institute of Life Sciences and Center for Research on Pain, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Raber
Pnina
P
Barbash
Shahar
S
Devor
Marshall
M
D000375:Aging / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D003714:Denervation; D005260:Female; D020022:Genetic Predisposition to Disease; D006614:Hindlimb / Q000294:innervation / Q000502:physiology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology*; D008026:Ligation; D008297:Male; D010146:Pain / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology*; D010147:Pain Measurement; D010523:Peripheral Nervous System Diseases / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology*; D010641:Phenotype; D010812:Physical Stimulation; D051381:Rats; D011917:Rats, Inbred Lew; D012727:Sex Characteristics; D013045:Species Specificity; D013127:Spinal Nerves / Q000293:injuries