Somatosensory behavioral alterations in a NGF-induced persistent low back pain model

Sex-Related Pain Behavioral Differences following Unilateral NGF Injections in a Rat Model of Low Back Pain

“…Behavior was measured at baseline, D0, (pre-1st injection); post-1st injection at selected time points, including D2 and D5 (pre-2nd injection); and post-2nd injection at D5 + 4 h, D7, D10, D14, D17, D21, D24, and D28. The established NGF model requires two injections to induce trunk pain [ 28 , 29 , 30 , 31 , 32 ]. The first injection induces an acute trunk pain response (hyperalgesia) that typically peaks by 2 days (D2) and returns to baseline by D5.…”

“…This acts as a priming effect so that after the second injection there is a prolonged hyperalgesia that is significant by 4 h and continues at least through D14 [ 28 , 29 , 30 ]. Behavioral assays were always performed from the least invasive to most invasive and from superficial to deep (i.e., cutaneous sensitivity testing prior to deep trunk algometer testing) in a similar fashion to quantitative sensory testing in humans [ 31 , 37 ].…”

“…Unfortunately, in these earlier unilateral NGF-LBP studies [ 28 , 29 , 30 ], the time to the resolution of NGF-related pain behaviors was not determined and female rats were not included, thereby preventing the characterization of potential sex differences (which are translationally relevant to clinical LBP). Thus, we recently expanded this unilateral NGF-LBP model by demonstrating that other somatosensory alterations, including delayed cutaneous mechanical hypersensitivity to touch, develop during this time course in male rats [ 31 ]. We conducted the first investigation using female rats in this NGF-LBP model [ 32 ], but the focus of this particular study was on the anti-hyperalgesic effects of simulated spinal manual therapy, and it contained no direct comparisons of female and male mechanical sensitivity.…”

“…We examined time-dependent differences in the baseline, onset, severity (i.e., the magnitude of change from baseline), laterality (i.e., ipsilateral and contralateral), and resolution of pain behavioral responses. The somatosensory behavioral assays performed in the NGF-LBP model were based on our previous study [ 31 ] and are similar to some of the standardized quantitative somatosensory tests typically performed in the low back and remote anatomical regions in clinical studies of LBP patients [ 35 , 36 ]. The mechanical sensitivity assays included remote (i.e., hindpaw) and local (i.e., trunk) cutaneous stimulation and local (i.e., trunk) deep muscle mechanical stimulation via algometer testing [ 31 ].…”

“…The somatosensory behavioral assays performed in the NGF-LBP model were based on our previous study [ 31 ] and are similar to some of the standardized quantitative somatosensory tests typically performed in the low back and remote anatomical regions in clinical studies of LBP patients [ 35 , 36 ]. The mechanical sensitivity assays included remote (i.e., hindpaw) and local (i.e., trunk) cutaneous stimulation and local (i.e., trunk) deep muscle mechanical stimulation via algometer testing [ 31 ]. A detailed characterization of altered LBP somatosensory behaviors in females with direct comparisons to males could provide important evidence for the potential of sex differences in LBP as well as guidance to investigations of the neurobiological mechanisms responsible for these phenomena.…”